doi: 10.1161/hc4601.099485
(Circulation. 2001;104:2673.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Endothelial Dysfunction, Oxidative Stress, and Risk of Cardiovascular Events in Patients With Coronary Artery Disease
From the Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Innere Medizin, Abteilung Kardiologie, Hamburg, Germany.
Correspondence to Thomas Heitzer, Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Innere Medizin, Abteilung Kardiologie, Martinistr 52, 20246 Hamburg, Germany. E-mail heitzer{at}uke.uni-hamburg.de
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background— Endothelial function is impaired in coronary artery disease and may contribute to its clinical manifestations. Increased oxidative stress has been linked to impaired endothelial function in atherosclerosis and may play a role in the pathogenesis of cardiovascular events. This study was designed to determine whether endothelial dysfunction and vascular oxidative stress have prognostic impact on cardiovascular event rates in patients with coronary artery disease.
Methods and Results— Endothelium-dependent and -independent vasodilation was determined in 281 patients with documented coronary artery disease by measuring forearm blood flow responses to acetylcholine and sodium nitroprusside using venous occlusion plethysmography. The effect of the coadministration of vitamin C (24 mg/min) was assessed in a subgroup of 179 patients. Cardiovascular events, including death from cardiovascular causes, myocardial infarction, ischemic stroke, coronary angioplasty, and coronary or peripheral bypass operation, were studied during a mean follow-up period of 4.5 years. Patients experiencing cardiovascular events (n=91) had lower vasodilator responses to acetylcholine (P<0.001) and sodium nitroprusside (P<0.05), but greater benefit from vitamin C (P<0.01). The Cox proportional regression analysis for conventional risk factors demonstrated that blunted acetylcholine-induced vasodilation (P=0.001), the effect of vitamin C (P=0.001), and age (P=0.016) remained independent predictors of cardiovascular events.
Conclusions— Endothelial dysfunction and increased vascular oxidative stress predict the risk of cardiovascular events in patients with coronary artery disease. These data support the concept that oxidative stress may contribute not only to endothelial dysfunction but also to coronary artery disease activity.
Key Words: antioxidants • coronary disease • endothelium • free radicals • prognosis
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The endothelium plays an integral role in the regulation of vascular tone, platelet activity, leukocyte adhesion, and thrombosis and is intimately involved in the development of atherosclerosis. Endothelial dysfunction has been observed in patients with established coronary artery disease or coronary risk factors, both in the coronary and peripheral vasculature.1 Therapeutic interventions with lipid-lowering drugs,2–4 ACE inhibitors,5 physical activity,6,7 and antioxidant agents3,8–10 have been shown to improve endothelial function in coronary and peripheral vessels. This systemic manifestation and improvement of endothelial function suggests that a common mechanism may contribute to endothelial dysfunction in the coronary and peripheral circulation. An increasing body of evidence suggests that increased oxidative stress accounts for a significant proportion of endothelial dysfunction. Increased production of oxygen-derived free radicals such as the superoxide anion has been linked to impaired endothelial vasomotor function in experimental models of atherosclerosis.11–13 Accordingly, treatment with antioxidants has been shown to improve coronary and peripheral endothelial function in patients with coronary artery disease or coronary risk factors.3,8–10,14
See p 2638
Less information is available about the prognostic impact of endothelial dysfunction and oxidative stress on atherosclerotic disease progression and cardiovascular risk. Very recent observations showed that depressed coronary vasoreactivity is associated with increased cardiovascular event rates.15,16 However, the mechanism(s) underlying this association between endothelial dysfunction and cardiovascular risk have not been defined.
Epidemiological studies indicate an association between increased intake of dietary antioxidants and reduced risk of coronary events.17–19 Thus, the hypothesis has been forwarded that an imbalance between increased oxidative stress and impaired antioxidant defense may not only affect endothelial function, but may also contribute to atherosclerotic disease progression. Therefore, we prospectively investigated whether systemic endothelial dysfunction and vascular oxidative stress, as assessed by the response to the antioxidant vitamin C, have prognostic impact on adverse long-term outcomes in patients with coronary artery disease.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Patient Population
Between January 1994 and October 1998, 281 consecutive patients who had been referred for assessment of coronary artery disease were studied prospectively. The inclusion criteria were angiographically documented coronary artery disease and a stable condition. Each subject was screened by a complete history, physical examination, and laboratory analysis. Exclusion criteria included unstable angina, recent myocardial infarction (<5 months), recent coronary angioplasty (<5 months), valvular heart disease, evidence of heart failure, uncontrolled hypertension, and/or significant endocrine, hepatic, renal, or inflammatory disease. Vasoactive medications, including calcium-channel blockers, ACE inhibitors, and long-acting nitrates, were withheld for
24 hours before the study. Patients were taking aspirin 100 mg/d on a long-term basis, with the exception of 11 patients who were taking clopidogrel. All female subjects were postmenopausal. Only 5 women were receiving hormone replacement therapy. Risk factors were assessed at the time of the endothelial function test. No caffeine intake or smoking was allowed before the study. The study was approved by the local ethics committee, and informed consent was obtained from all participants.
Assessment of Vascular Function
All studies were performed after a 12-hour overnight fast with the subjects lying supine in a quiet, temperature-controlled room (22°C to 24°C). Using sterile conditions and 2% lidocaine, a 20-gauge polyethylene catheter was inserted into the brachial artery of the nondominant arm to measure blood pressure and drug infusion. Forearm blood flow (FBF) was measured by venous occlusion plethysmography with calibrated mercury-in-silastic strain gauges, as previously described.10 During FBF measurement, circulation to the hand was excluded by a wrist cuff that was inflated to 40 mm Hg above systolic blood pressure. At the beginning of each study protocol, normal saline (0.9% sodium chloride) was infused intra-arterially at a rate of 0.4 mL/min. Endothelium-dependent vasodilation was assessed by infusing acetylcholine (ACh) in increasing concentrations of 7.5, 15, and 30 µg/min (ACh1 to 3) into the brachial artery. Sodium nitroprusside (SNP) was infused to assess endothelium-independent vasodilation (1, 3, and 10 µg/min). The sequence of ACh and SNP infusion was randomized. In a subgroup of 179 patients, the dose-response curve to ACh was repeated during coinfusion of vitamin C at 24 mg/min. This dose of vitamin C was chosen to provide a final plasma concentration of 
10 mmol/L.8,20 Vitamin C infusion was started 10 minutes before ACh infusion and was continued throughout. Finally, the dose-response curve to SNP was repeated during coinfusion with vitamin C. A 30-minute washout was allowed between each dose-response curve.
Long-Term Follow-Up
Follow-up data were obtained using questionnaires sent to patients and/or primary physicians. In addition, hospital records were reviewed. During long-term follow-up, the following events were assessed. Death from cardiovascular causes was defined as death due to a myocardial or cerebral infarction or documented sudden cardiac death. Myocardial infarction, ischemic stroke, PTCA, CABG, and peripheral bypass revascularization were confirmed by reviewing hospital records. Medical therapy, especially with ACE inhibitors, lipid-lowering drugs, and antioxidants, was documented.
Statistical Analysis
Data of baseline characteristics and cardiovascular events at follow-up are expressed as mean±SD or n (%). Responses to ACh and SNP, with and without vitamin C, are presented as mean±SEM and were analyzed by ANOVA for repeated measures. Scheffe’s test was applied for multiple comparison testing.
Cumulative event rates were estimated by Kaplan-Meier survival curves, and probability values were determined with the log-rank test. For Kaplan-Meier analyses, ACh- and SNP-induced vasodilation and the effect of vitamin C were divided into values below and above the median. Cox proportional hazards regression analysis was performed to determine independent predictors of cardiovascular events for all patients studied. This Cox model included the following variables: age; sex; the presence of hypertension; smoking; diabetes; previous infarction; serum levels of total cholesterol, LDL cholesterol, and HDL cholesterol; extent of vessel disease; and FBF responses to ACh and SNP. An additional Cox regression analysis was performed for the subgroup of patients who also received vitamin C. P<0.05 was considered statistically significant.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Patient Characteristics
We included 281 patients in the study. Of these, 5 patients were excluded because follow-up could not be done. The baseline characteristics of the remaining 276 patients are summarized in Table 1. Patients were followed for a mean of 53 months (range, 30 to 87 months). At follow-up, we documented 120 cardiovascular events in 91 patients (Table 2). Sixty-nine patients experienced 1 event, 15 patients had 2 events, and 7 patients had 3 events. In addition, 3 patients died of cancer.
|
|
On univariate analysis, only age (P=0.01) and diabetes (P=0.03) were significantly associated with the occurrence of cardiovascular events. The use of ACE inhibitors, lipid-lowering agents, and antioxidants was comparable between groups with and without cardiovascular events.
Peripheral Vascular Function and Prognosis
Intra-arterial infusion of ACh increased FBF in the total group of patients from a basal FBF of 2.7±0.1 mL/min per 100 mL to 5.8±0.1 (ACh1), 8.3±0.2 (ACh2), and (maximally) 11.7±0.3 mL/min per 100 mL of tissue (ACh3). Patients experiencing cardiovascular events during follow-up had a significantly lower vasodilator response compared with patients without events (P<0.001 by ANOVA). In patients with events, ACh1-induced FBF was 4.7±0.2 mL/min per 100 mL (6.1±0.2 mL/min per 100 mL in patients without events) and ACh2-induced FBF was 6.5±0.3 mL/min per 100 mL (9.1±0.3 mL/min per 100 mL in patients without events). The FBF responses to ACh3 are illustrated in Figure 1A. There were significant differences between patients with and without cardiovascular events.
|
The intra-arterial infusion of SNP increased FBF in the total group from 2.7±0.1 mL/min per 100 mL to 5.7±0.2 (SNP1), 9.5±0.2 (SNP2), and 14.2±0.2 mL/min per 100 mL (SNP3). The vasodilator response to SNP was slightly but significantly reduced in patients with cardiovascular events compared with patients free of events (P<0.05 by ANOVA). In patients with events, SNP1-induced FBF was 5.6±0.2 mL/min per 100 mL (5.9±0.3 mL/min per 100 mL in patients without events), and SNP2-induced FBF was 9.2±0.4 mL/min per 100 mL (9.9±0.3 mL/min per 100 mL in patients without events). The FBF responses to SNP3 are illustrated in Figure 1B. Again, these responses showed slightly, but significantly, reduced FBF responses in patients with events.
The cumulative proportion of patients with cardiovascular events according to the vasodilator response to ACh and SNP is shown in Figure 2. The incidence of cardiovascular events increased significantly with decreasing vasodilator response to ACh (Figure 2A). There was a small but significant increase in cardiovascular events with decreasing vasodilator response to SNP (Figure 2B).
|
Effect of Vitamin C and Prognosis
A subgroup of 179 patients received an intra-arterial infusion of vitamin C and was followed for a mean of 45 months (range, 31 to 74 months). At follow-up, 67 cardiovascular events occurred in 49 patients. The vasodilator response to ACh was significantly lower in patients experiencing cardiovascular events compared with patients without events (Figure 3A). Coinfusion of vitamin C improved FBF responses to ACh in patients with and without events. However, the effect of vitamin C was significantly larger in patients experiencing cardiovascular events during follow-up compared with patients without events (P<0.01 by ANOVA). Using Kaplan-Meier analyses, the incidence of cardiovascular events increased significantly with increasing effect of vitamin C on ACh-induced FBF (Figure 3B). Infusion of vitamin C had no significant effect on SNP-induced vasodilation in patients with and without events.
|
Cox Regression Analysis
Cox proportional hazards regression was used to analyze follow-up data and to determine independent predictors of cardiovascular events. Analysis for all patients (n=276) included the following variables: age, sex, the presence of hypertension, smoking, diabetes, previous infarction, serum levels of cholesterol (total, LDL, and HDL), extent of vessel disease, and FBF responses to ACh and SNP. In this analysis, ACh-induced vasodilation (P<0.001) and age (P=0.002) were significantly associated with the occurrence of cardiovascular events. Diabetes (P=0.09) and smoking (P=0.15) did not reach significance (Table 3). In addition, Cox regression analysis for the subgroup of patients investigated with vitamin C (n=179) was performed. When the vitamin C effect on ACh-response was included into the regression analysis, the remaining independent predictors of cardiovascular events were ACh-induced vasodilation (P=0.001), effect of vitamin C on ACh-response (P=0.001), and age (P=0.016) (Table 4).
|
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Endothelium-dependent vasodilation has been shown to be impaired in patients with atherosclerosis or risk factors for atherosclerosis. Numerous studies have demonstrated that this impairment occurs in both the coronary and peripheral circulation.8,9,21,22 Although the correlation between the coronary and peripheral circulation is reported to be only modest,21,23 common underlying mechanism(s) seem to account for the observed depression of endothelial function. This suggestion of a systemic nature of endothelial dysfunction is further supported by the observation that different therapeutic interventions such as lipid-lowering,2,4 ACE inhibition,5 physical activit,y6,7 and antioxidant therapy3,8–10 exert their beneficial effects on both the coronary and peripheral circulation.
In experimental animal models of atherosclerosis, hypercholesterolemia, hypertension, and diabetes, associations between oxidative stress and impaired endothelial function have been demonstrated.11–13 Among many biological changes that occur in the vessel wall under these conditions, reduced bioavailability of nitric oxide (NO) in a setting of increased superoxide anion levels seems to be a uniform underlying abnormality. Recent studies extended this potential mechanism to patients with coronary artery disease by demonstrating increased superoxide production of human blood vessels in association with endothelial vasomotor dysfunction and with clinical risk factors.24,25 Furthermore, endothelial dysfunction in patients with coronary artery disease or coronary risk factors could be reversed by the administration of agents capable of scavenging superoxide, such as vitamin C.8–10,20 These findings suggest that increased oxidative stress may be an important mechanism for impaired endothelial function in patients with atherosclerosis or cardiovascular risk factors.
There is a paucity of information regarding the role of endothelial dysfunction on the progression of atherosclerotic disease and the cardiovascular event rate. Very recent studies indicate that abnormal coronary vasoreactivity in patients with coronary artery disease is a predictor of increased cardiovascular risk.15,16 The present study extends these observations to the systemic circulation of patients with coronary disease. Our data indicate that peripheral endothelial vasodilator dysfunction is associated with increased cardiovascular risk and may serve as an independent predictor of atherosclerotic disease activity. These findings are in line with a recent investigation demonstrating the prognostic value of endothelium-dependent vasodilation in the brachial artery.26 Patients in these studies had only mild coronary artery disease, and therefore the event rate was low.26 We included patients with well-established coronary vessel disease and found an event rate comparable to those of other follow-up studies in patients with CAD.27
The mechanisms responsible for the association between impaired endothelial function and the progression of atherosclerotic disease are unknown. After finding a similar relationship between abnormal coronary vasodilator response and the long-term outcome of coronary heart disease, Schachinger et al16 speculated that a blunted dilator response mirrors the oxidative stress imposed on the vascular wall, which in turn will determine disease activity. In fact, the present study underscores this potential mechanism of oxidative stress–driven progression of atherosclerotic disease, because the beneficial effect of vitamin C was significantly increased in patients who experienced cardiovascular events. The oxygen-derived free radical superoxide combines with NO in a diffusion-limited reaction (k=6.7x1010 mol/L per s) that is 3 times faster than the dismutation of superoxide by superoxide dismutase. This reaction produces peroxynitrite, a compound with limited NO-like bioactivity, thereby "shunting" NO away from its typical targets, such as vasodilation and inhibition of platelets. This latter effect may be important for triggering vascular events because impaired NO bioactivity is predictive of atherosclerotic disease activity.28
Vitamin C is an extremely effective antioxidant, and it is an efficient scavenger of many reactive oxygen species, including superoxide anions29 and peroxynitrite. We and others have demonstrated that the beneficial effect of vitamin C at 24 mg/min on endothelial dysfunction in patients with risk factors or coronary artery disease is specific, because it was observed neither in healthy control subjects nor on the endothelium-independent vasodilation induced by SNP or nitroglycerin.8–10 Thus, the results of these studies are consistent with the concept that the scavenging of increased oxygen-derived free radicals may account for the beneficial effects of vitamin C in these settings. The salient finding of the present study is that the positive response to vitamin C was an independent predictor of a higher risk of cardiovascular events. This observation supports the concept that oxidative stress contributes to the progression of atherosclerotic disease and may, therefore, be an important determinant of clinical events.
Given the conflicting data from clinical trials of antioxidants in cardiovascular disease, the emergence of such a clear result may seem quite a surprise. As mentioned above, however, it is a quite consistent finding that vitamin C can improve endothelial dysfunction in diseases where oxidative stress may play a role, such as hypercholesterolemia, long-term smoking, congestive heart failure, hypertension, and diabetes mellitus. Therefore, we think that vitamin C’s effects on ACh-induced vasodilation can be used as a surrogate parameter reflecting oxidative stress in vascular tissue. On the basis of the very low rate constant of the reaction between vitamin C and superoxide (k=3x105 mol/L per s), vitamin C must be given in very high concentrations to compete successfully with NO for superoxide anion. Accordingly, high concentrations of vitamin C have to be given intra-arterially in these protocols. Although we can improve endothelial dysfunction with this approach in the short-term, it may also be easy to understand why therapies with oral vitamin C have been shown to be rather unsuccessful.
In the present study, we also found that endothelium-independent vasodilation to SNP was mildly impaired in patients experiencing cardiovascular events compared with patients without events. Interestingly, in the setting of hypercholesterolemia, superoxide has also been shown to be increased in endothelial cells and in smooth muscle cells,28 which in turn may inhibit the activity of the NO target enzyme, soluble guanylyl cyclase.30 In addition, a recent investigation demonstrated that vascular oxidative stress is associated with a reversible impairment of activity of the cGMP-dependent protein kinase, leading to reduced NO/cGMP-dependent relaxation.31
Noteworthy is the growing evidence for a common pathway mediating oxidative stress, vascular dysfunction, and inflammatory gene induction.32 Recent studies demonstrated that a systemic inflammatory response leads to an impairment of endothelial function in both resistance and conduit vessels.33 Furthermore, blunted systemic endothelial vasoreactivity was found to be related to elevated plasma levels of C-reactive protein in patients with coronary artery disease.34 On the basis of these observations, we conclude that changes in endothelial activity may emphasize the link between inflammation and the risk of cardiovascular events.
In conclusion, the present study demonstrates that blunted systemic endothelial vasoreactivity represents an independent predictor for increased cardiovascular risk. Although no measures of endogenous antioxidant defense or of oxidant stress in plasma were performed, we think that increased vascular oxidative stress, as indicated by the higher response to vitamin C, may represent an important underlying mechanism for endothelial dysfunction and for the pathogenesis of cardiovascular events.
|
Acknowledgments |
|---|
We would like to thank Volker Schoder for helpful assistance with statistical analyses.
Received July 23, 2001; revision received September 17, 2001; accepted September 18, 2001.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Drexler H. Endothelial dysfunction: clinical implications. Prog Cardiovasc Dis.. 1997; 39: 287–324.[Medline] [Order article via Infotrieve]
2.
Treasure CB, Klein JL, Weintraub WS, et al. Beneficial effects of cholesterol-lowering therapy on the coronary endothelium in patients with coronary artery disease. N Engl J Med.. 1995; 332: 481–487.
3.
Anderson TJ, Meredith IT, Yeung AC, et al. The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion. N Engl J Med.. 1995; 332: 488–493.
4. Stroes ES, Koomans HA, de Bruin TW, et al. Vascular function in the forearm of hypercholesterolaemic patients off and on lipid-lowering medication. Lancet.. 1995; 346: 467–471.[Medline] [Order article via Infotrieve]
5.
Mancini GB, Henry GC, Macaya C, et al. Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease: the TREND (Trial on Reversing ENdothelial Dysfunction) study [published erratum appears in Circulation. 1996;94:1490]. Circulation.. 1996; 94: 258–265.
6.
Hambrecht R, Wolf A, Gielen S, et al. Effect of exercise on coronary endothelial function in patients with coronary artery disease. N Engl J Med.. 2000; 342: 454–460.
7.
Hornig B, Maier V, Drexler H. Physical training improves endothelial function in patients with chronic heart failure. Circulation.. 1996; 93: 210–214.
8.
Ting HH, Timimi FK, Haley EA, et al. Vitamin C improves endothelium-dependent vasodilation in forearm resistance vessels of humans with hypercholesterolemia. Circulation.. 1997; 95: 2617–2622.
9.
Levine GN, Frei B, Koulouris SN, et al. Ascorbic acid reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation.. 1996; 93: 1107–1113.
10.
Heitzer T, Just H, Munzel T. Antioxidant vitamin C improves endothelial dysfunction in chronic smokers. Circulation.. 1996; 94: 6–9.
11. Ohara Y, Peterson TE, Harrison DG. Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest.. 1993; 91: 2546–2551.
12. Keaney JF,Jr, Vita JA. Atherosclerosis, oxidative stress, and antioxidant protection in endothelium-derived relaxing factor action. Prog Cardiovasc Dis.. 1995; 38: 129–154.[Medline] [Order article via Infotrieve]
13.
Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res.. 2000; 87: 840–844.
14.
Gokce N, Keaney JFJr, Frei B, et al. Long-term ascorbic acid administration reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation.. 1999; 99: 3234–3240.
15.
Suwaidi JA, Hamasaki S, Higano ST, et al. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation.. 2000; 101: 948–954.
16.
Schachinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation.. 2000; 101: 1899–1906.
17.
Kushi LH, Folsom AR, Prineas RJ, et al. Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women. N Engl J Med.. 1996; 334: 1156–1162.
18.
Rimm EB, Stampfer MJ, Ascherio A, et al. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med.. 1993; 328: 1450–1456.
19. Enstrom JE, Kanim LE, Klein MA. Vitamin C intake and mortality among a sample of the United States population. Epidemiology.. 1992; 3: 194–202.[Medline] [Order article via Infotrieve]
20.
Jackson TS, Xu A, Vita JA, et al. Ascorbate prevents the interaction of superoxide and nitric oxide only at very high physiological concentrations. Circ Res.. 1998; 83: 916–922.
21. Anderson TJ, Uehata A, Gerhard MD, et al. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol.. 1995; 26: 1235–1241.[Abstract]
22.
Heitzer T, Yla Herttuala S, Wild E, et al. Effect of vitamin E on endothelial vasodilator function in patients with hypercholesterolemia, chronic smoking or both. J Am Coll Cardiol.. 1999; 33: 499–505.
23. Neunteufl T, Katzenschlager R, Hassan A, et al. Systemic endothelial dysfunction is related to the extent and severity of coronary artery disease. Atherosclerosis.. 1997; 129: 111–118.[Medline] [Order article via Infotrieve]
24. Guzik TJ, West NE, Black E, et al. Vascular superoxide production by NAD(P)H oxidase: association with endothelial dysfunction and clinical risk factors. Circ Res.. 2000; 86: e85–e90.
25.
Huraux C, Makita T, Kurz S, et al. Superoxide production, risk factors, and endothelium-dependent relaxations in human internal mammary arteries. Circulation.. 1999; 99: 53–59.
26. Neunteufl T, Heher S, Katzenschlager R, et al. Late prognostic value of flow-mediated dilation in the brachial artery of patients with chest pain. Am J Cardiol.. 2000; 86: 207–210.[Medline] [Order article via Infotrieve]
27.
Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients: the Heart Outcomes Prevention Evaluation Study Investigators [published erratum appears in N Engl J Med. 2000;342:748]. N Engl J Med.. 2000; 342: 145–153.
28.
Miller FJJr, Gutterman DD, Rios CD, et al. Superoxide production in vascular smooth muscle contributes to oxidative stress and impaired relaxation in atherosclerosis. Circ Res.. 1998; 82: 1298–1305.
29.
Frei B, England L, Ames BN. Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci U S A. 1989; 86: 6377–6381.
30. Mulsch A, Bauersachs J, Schafer A, et al. Effect of YC-1, an NO-independent, superoxide-sensitive stimulator of soluble guanylyl cyclase, on smooth muscle responsiveness to nitrovasodilators. Br J Pharmacol.. 1997; 120: 681–689.[Medline] [Order article via Infotrieve]
31.
Oelze M, Mollnau H, Hoffmann N, et al. Vasodilator-stimulated phosphoprotein serine 239 phosphorylation as a sensitive monitor of defective nitric oxide/cGMP signaling and endothelial dysfunction. Circ Res.. 2000; 87: 999–1005.
32. Liao F, Andalibi A, Qiao JH, et al. Genetic evidence for a common pathway mediating oxidative stress, inflammatory gene induction, and aortic fatty streak formation in mice. J Clin Invest.. 1994; 94: 877–884.
33.
Hingorani AD, Cross J, Kharbanda RK, et al. Acute systemic inflammation impairs endothelium-dependent dilatation in humans. Circulation.. 2000; 102: 994–999.
34.
Fichtlscherer S, Rosenberger G, Walter DH, et al. Elevated C-reactive protein levels and impaired endothelial vasoreactivity in patients with coronary artery disease. Circulation.. 2000; 102: 1000–1006.
This article has been cited by other articles:
 |
|
 |
|
  A. Ceriello and R. Testa Antioxidant Anti-Inflammatory Treatment in Type 2 Diabetes Diabetes Care, November 1, 2009; 32(suppl_2): S232 - S236. [Full Text] [PDF]
|
|
|
|
 |
|
 F. Violi, V. Sanguigni, R. Carnevale, A. Plebani, P. Rossi, A. Finocchi, C. Pignata, D. De Mattia, B. Martire, M. C. Pietrogrande, et al. Hereditary Deficiency of gp91phox Is Associated With Enhanced Arterial Dilatation: Results of a Multicenter Study Circulation, October 20, 2009; 120(16): 1616 - 1622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Munzel and T. Gori Nebivolol The Somewhat-Different beta-Adrenergic Receptor Blocker. J. Am. Coll. Cardiol., October 13, 2009; 54(16): 1491 - 1499. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Gluba, M. Banach, J. Rysz, G. Piotrowski, W. Fendler, and T. Pietrucha Is Polymorphism Within eNOS Gene Associated With the Late Onset of Myocardial Infarction? A Pilot Study Angiology, October 1, 2009; 60(5): 588 - 595. [Abstract] [PDF]
|
|
|
|
|
|
J. Xu and M.-H. Zou Molecular Insights and Therapeutic Targets for Diabetic Endothelial Dysfunction Circulation, September 29, 2009; 120(13): 1266 - 1286. [Full Text] [PDF]
|
|
|
|
 |
|
 N. Koivuviita, R. Tertti, M. Jarvisalo, M. Pietila, J. Hannukainen, J. Sundell, P. Nuutila, J. Knuuti, and K. Metsarinne Increased basal myocardial perfusion in patients with chronic kidney disease without symptomatic coronary artery disease Nephrol. Dial. Transplant., September 1, 2009; 24(9): 2773 - 2779. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Leon and U. G. Bronas Pathophysiology of Coronary Heart Disease and Biological Mechanisms for the Cardioprotective Effects of Regular Aerobic Exercise American Journal of Lifestyle Medicine, September 1, 2009; 3(5): 379 - 385. [Abstract] [PDF]
|
|
|
|
 |
|
 J. Xu, S. Wang, Y. Wu, P. Song, and M.-H. Zou Tyrosine Nitration of PA700 Activates the 26S Proteasome to Induce Endothelial Dysfunction in Mice With Angiotensin II-Induced Hypertension Hypertension, September 1, 2009; 54(3): 625 - 632. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-C. Tardif Angiotensin-converting enzyme inhibitors and atherosclerotic plaque: a key role in the cardiovascular protection of patients with coronary artery disease Eur. Heart J. Suppl., August 1, 2009; 11(suppl_E): E9 - E16. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Calvert and D. J. Lefer Myocardial protection by nitrite Cardiovasc Res, July 15, 2009; 83(2): 195 - 203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Spiekermann, K. Schenk, and M. M. Hoeper Increased xanthine oxidase activity in idiopathic pulmonary arterial hypertension Eur. Respir. J., July 1, 2009; 34(1): 276 - 276. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ahmed, T. Fujisawa, X.-L. Niu, S. Ahmad, B. Al-Ani, K. Chudasama, A. Abbas, R. Potluri, V. Bhandari, C. M. Findley, et al. Angiopoietin-2 Confers Atheroprotection in apoE-/- Mice by Inhibiting LDL Oxidation via Nitric Oxide Circ. Res., June 19, 2009; 104(12): 1333 - 1336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Perrier, M.-P. Fournet-Bourguignon, E. Royere, S. Molez, H. Reure, L. Lesage, W. Gosgnach, Y. Frapart, J.-L. Boucher, N. Villeneuve, et al. Effect of uncoupling endothelial nitric oxide synthase on calcium homeostasis in aged porcine endothelial cells Cardiovasc Res, April 1, 2009; 82(1): 133 - 142. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. C. Hawkes and L. J. Laslett Selenium supplementation does not improve vascular responsiveness in healthy North American men Am J Physiol Heart Circ Physiol, February 1, 2009; 296(2): H256 - H262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Yuditskaya, A. Tumblin, G. T. Hoehn, G. Wang, S. K. Drake, X. Xu, S. Ying, A. H. Chi, A. T. Remaley, R.-F. Shen, et al. Proteomic identification of altered apolipoprotein patterns in pulmonary hypertension and vasculopathy of sickle cell disease Blood, January 29, 2009; 113(5): 1122 - 1128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kitta, J.-e. Obata, T. Nakamura, M. Hirano, Y. Kodama, D. Fujioka, Y. Saito, K.-i. Kawabata, K. Sano, T. Kobayashi, et al. Persistent impairment of endothelial vasomotor function has a negative impact on outcome in patients with coronary artery disease. J. Am. Coll. Cardiol., January 27, 2009; 53(4): 323 - 330. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Volzke, D. M. Robinson, T. Spielhagen, M. Nauck, A. Obst, R. Ewert, B. Wolff, H. Wallaschofski, S. B. Felix, and M. Dorr Are serum thyrotropin levels within the reference range associated with endothelial function? Eur. Heart J., January 2, 2009; 30(2): 217 - 224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Joras and P. Poredos The association of acute exercise-induced ischaemia with systemic vasodilator function in patients with peripheral arterial disease Vascular Medicine, November 1, 2008; 13(4): 255 - 262. [Abstract] [PDF]
|
|
|
|
|
|
A. R. Pries, H. Habazettl, G. Ambrosio, P. R. Hansen, J. C. Kaski, V. Schachinger, H. Tillmanns, G. Vassalli, I. Tritto, M. Weis, et al. A review of methods for assessment of coronary microvascular disease in both clinical and experimental settings Cardiovasc Res, November 1, 2008; 80(2): 165 - 174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Galle, E. Schwedhelm, S. Pinnetti, R. H. Boger, C. Wanner, and on behalf of the VIVALDI investigators Antiproteinuric effects of angiotensin receptor blockers: telmisartan versus valsartan in hypertensive patients with type 2 diabetes mellitus and overt nephropathy Nephrol. Dial. Transplant., October 1, 2008; 23(10): 3174 - 3183. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Donato, I. Eskurza, K. L. Jablonski, L. B. Gano, G. L. Pierce, and D. R. Seals Cytochrome P-450 2C9 signaling does not contribute to age-associated vascular endothelial dysfunction in humans J Appl Physiol, October 1, 2008; 105(4): 1359 - 1363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. K. Rao and J. R. Bender Rac, PAK, and eNOS ACTion Circ. Res., August 15, 2008; 103(4): 328 - 330. [Full Text] [PDF]
|
|
|
|
|
|
B. Fernhall and S. Agiovlasitis Arterial function in youth: window into cardiovascular risk J Appl Physiol, July 1, 2008; 105(1): 325 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D Tousoulis, M Charakida, and C Stefanadis Endothelial function and inflammation in coronary artery disease Postgrad. Med. J., July 1, 2008; 84(993): 368 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. L. Pierce, S. D. Beske, B. R. Lawson, K. L. Southall, F. J. Benay, A. J. Donato, and D. R. Seals Weight Loss Alone Improves Conduit and Resistance Artery Endothelial Function in Young and Older Overweight/Obese Adults Hypertension, July 1, 2008; 52(1): 72 - 79. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Jabs, S. Gobel, P. Wenzel, A. L. Kleschyov, M. Hortmann, M. Oelze, A. Daiber, and T. Munzel Sirolimus-induced vascular dysfunction increased mitochondrial and nicotinamide adenosine dinucleotide phosphate oxidase-dependent superoxide production and decreased vascular nitric oxide formation. J. Am. Coll. Cardiol., June 3, 2008; 51(22): 2130 - 2138. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Pizzi, L. Manzoli, S. Mancini, and G. M. Costa Analysis of potential predictors of depression among coronary heart disease risk factors including heart rate variability, markers of inflammation, and endothelial function Eur. Heart J., May 1, 2008; 29(9): 1110 - 1117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Crabtree, C. L. Smith, G. Lam, M. S. Goligorsky, and S. S. Gross Ratio of 5,6,7,8-tetrahydrobiopterin to 7,8-dihydrobiopterin in endothelial cells determines glucose-elicited changes in NO vs. superoxide production by eNOS Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1530 - H1540. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. V. Brauner, L. Forchhammer, P. Moller, L. Barregard, L. Gunnarsen, A. Afshari, P. Wahlin, M. Glasius, L. O. Dragsted, S. Basu, et al. Indoor Particles Affect Vascular Function in the Aged: An Air Filtration-based Intervention Study Am. J. Respir. Crit. Care Med., February 15, 2008; 177(4): 419 - 425. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Schiffrin Oxidative Stress, Nitric Oxide Synthase, and Superoxide Dismutase: A Matter of Imbalance Underlies Endothelial Dysfunction in the Human Coronary Circulation Hypertension, January 1, 2008; 51(1): 31 - 32. [Full Text] [PDF]
|
|
|
|
|
|
M. Briet, C. Collin, S. Laurent, A. Tan, M. Azizi, M. Agharazii, X. Jeunemaitre, F. Alhenc-Gelas, and P. Boutouyrie Endothelial Function and Chronic Exposure to Air Pollution in Normal Male Subjects Hypertension, November 1, 2007; 50(5): 970 - 976. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-H. Chan, K.-K. Lau, K.-H. Yiu, S.-W. Li, H.-T. Chan, S. Tam, X.-O. Shu, C.-P. Lau, and H.-F. Tse Isoflavone intake in persons at high risk of cardiovascular events: implications for vascular endothelial function and the carotid atherosclerotic burden Am. J. Clinical Nutrition, October 1, 2007; 86(4): 938 - 945. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Philpott and T. J. Anderson Reactive Hyperemia and Cardiovascular Risk Arterioscler Thromb Vasc Biol, October 1, 2007; 27(10): 2065 - 2067. [Full Text] [PDF]
|
|
|
|
|
|
A. L. Huang, A. E. Silver, E. Shvenke, D. W. Schopfer, E. Jahangir, M. A. Titas, A. Shpilman, J. O. Menzoian, M. T. Watkins, J. D. Raffetto, et al. Predictive Value of Reactive Hyperemia for Cardiovascular Events in Patients With Peripheral Arterial Disease Undergoing Vascular Surgery Arterioscler Thromb Vasc Biol, October 1, 2007; 27(10): 2113 - 2119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Schnabel and S. Blankenberg Oxidative Stress in Cardiovascular Disease: Successful Translation From Bench to Bedside? Circulation, September 18, 2007; 116(12): 1338 - 1340. [Full Text] [PDF]
|
|
|
|
|
|
H. Tornqvist, N. L. Mills, M. Gonzalez, M. R. Miller, S. D. Robinson, I. L. Megson, W. MacNee, K. Donaldson, S. Soderberg, D. E. Newby, et al. Persistent Endothelial Dysfunction in Humans after Diesel Exhaust Inhalation Am. J. Respir. Crit. Care Med., August 15, 2007; 176(4): 395 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Shenouda and J. A. Vita Effects of Flavonoid-Containing Beverages and EGCG on Endothelial Function J. Am. Coll. Nutr., August 1, 2007; 26(4): 366S - 372S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sherwood, J. K. Bower, J. McFetridge-Durdle, J. A. Blumenthal, L. K. Newby, and A. L. Hinderliter Age Moderates the Short-Term Effects of Transdermal 17{beta}-Estradiol on Endothelium-Dependent Vascular Function in Postmenopausal Women Arterioscler Thromb Vasc Biol, August 1, 2007; 27(8): 1782 - 1787. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Mittermayer, G. Schaller, J. Pleiner, K. Krzyzanowska, S. Kapiotis, M. Roden, and M. Wolzt Rosiglitazone Prevents Free Fatty Acid-Induced Vascular Endothelial Dysfunction J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2574 - 2580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Robinson, C. A. Ludlam, N. A. Boon, and D. E. Newby Endothelial Fibrinolytic Capacity Predicts Future Adverse Cardiovascular Events in Patients With Coronary Heart Disease Arterioscler Thromb Vasc Biol, July 1, 2007; 27(7): 1651 - 1656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Junor and K. C. Dellsperger Can we use surrogate vascular beds for evaluating endothelial function of the coronary vasculature in patients with cardiac allografts? Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H13 - H14. [Full Text] [PDF]
|
|
|
|
|
|
Authors/Task Force Members:, G. Mancia, G. De Backer, A. Dominiczak, R. Cifkova, R. Fagard, G. Germano, G. Grassi, A. M. Heagerty, S. E. Kjeldsen, et al. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) Eur. Heart J., June 11, 2007; (2007) ehm236v1. [Full Text] [PDF]
|
|
|
|
 |
|
 N. Marx and P. J Grant Endothelial dysfunction and cardiovascular disease - the lull before the storm Diabetes and Vascular Disease Research, June 1, 2007; 4(2): 82 - 83. [PDF]
|
|
|
|
|
|
R. E. Schmieder, C. Delles, A. Mimran, J. P. Fauvel, and L. M. Ruilope Impact of Telmisartan Versus Ramipril on Renal Endothelial Function in Patients With Hypertension and Type 2 Diabetes Diabetes Care, June 1, 2007; 30(6): 1351 - 1356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Anderson Prognostic Significance of Brachial Flow-Mediated Vasodilation Circulation, May 8, 2007; 115(18): 2373 - 2375. [Full Text] [PDF]
|
|
|
|
|
|
R. Belardinelli, M. Solenghi, L. Volpe, and A. Purcaro Trimetazidine improves endothelial dysfunction in chronic heart failure: an antioxidant effect Eur. Heart J., May 1, 2007; 28(9): 1102 - 1108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Landmesser, S. Spiekermann, C. Preuss, S. Sorrentino, D. Fischer, C. Manes, M. Mueller, and H. Drexler Angiotensin II Induces Endothelial Xanthine Oxidase Activation: Role for Endothelial Dysfunction in Patients With Coronary Disease Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): 943 - 948. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hattori, S. Hattori, X. Wang, H. Satoh, N. Nakanishi, and K. Kasai Oral Administration of Tetrahydrobiopterin Slows the Progression of Atherosclerosis in Apolipoprotein E-Knockout Mice Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): 865 - 870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Barac, U. Campia, and J. A. Panza Methods for Evaluating Endothelial Function in Humans Hypertension, April 1, 2007; 49(4): 748 - 760. [Full Text] [PDF]
|
|
|
|
|
|
T. Munzel, P. Wenzel, and A. Daiber Do We Still Need Organic Nitrates? J. Am. Coll. Cardiol., March 27, 2007; 49(12): 1296 - 1298. [Full Text] [PDF]
|
|
|
|
|
|
G. R. Thomas, J. M. DiFabio, T. Gori, and J. D. Parker Once Daily Therapy With Isosorbide-5-Mononitrate Causes Endothelial Dysfunction in Humans: Evidence of a Free-Radical-Mediated Mechanism J. Am. Coll. Cardiol., March 27, 2007; 49(12): 1289 - 1295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Lee, C. Shirodaria, C. E Jackson, M. D Robson, C. Antoniades, J. M Francis, F. Wiesmann, K. M Channon, S. Neubauer, and R. P Choudhury Multi-modal magnetic resonance imaging quantifies atherosclerosis and vascular dysfunction in patients with type 2 diabetes mellitus Diabetes and Vascular Disease Research, March 1, 2007; 4(1): 44 - 48. [Abstract] [PDF]
|
|
|
|
 |
|
 N. Toda, K. Ayajiki, and T. Okamura Interaction of Endothelial Nitric Oxide and Angiotensin in the Circulation Pharmacol. Rev., March 1, 2007; 59(1): 54 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Noma, C. Goto, K. Nishioka, D. Jitsuiki, T. Umemura, K. Ueda, M. Kimura, K. Nakagawa, T. Oshima, K. Chayama, et al. Roles of Rho-Associated Kinase and Oxidative Stress in the Pathogenesis of Aortic Stiffness J. Am. Coll. Cardiol., February 13, 2007; 49(6): 698 - 705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. T. Sezgin, I. Barutcu, N. Sezgin, H. Gullu, A. M. Esen, N. Acikgoz, E. Topal, and R. Ozdemir Contribution of Plasma Lipid Disturbances to Vascular Endothelial Function in Patients With Slow Coronary Flow Angiology, January 1, 2007; 57(6): 694 - 701. [Abstract] [PDF]
|
|
|
|
|
|
N. Stadler, J. Eggermann, S. Voo, A. Kranz, and J. Waltenberger Smoking-Induced Monocyte Dysfunction Is Reversed by Vitamin C Supplementation In Vivo Arterioscler Thromb Vasc Biol, January 1, 2007; 27(1): 120 - 126. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Adlam, J. K. Bendall, J. P. De Bono, N. J. Alp, J. Khoo, T. Nicoli, M. Yokoyama, S. Kawashima, and K. M. Channon Cardiovascular Control: Relationships between nitric oxide-mediated endothelial function, eNOS coupling and blood pressure revealed by eNOS-GTP cyclohydrolase 1 double transgenic mice Exp Physiol, January 1, 2007; 92(1): 119 - 126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. George, E. Carr, J. Davies, J.J.F. Belch, and A. Struthers High-Dose Allopurinol Improves Endothelial Function by Profoundly Reducing Vascular Oxidative Stress and Not by Lowering Uric Acid Circulation, December 5, 2006; 114(23): 2508 - 2516. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K W Lee, A D Blann, K Jolly, G Y H Lip, and on behalf of the BRUM Investigators Plasma haemostatic markers, endothelial function and ambulatory blood pressure changes with home versus hospital cardiac rehabilitation: the Birmingham Rehabilitation Uptake Maximisation Study Heart, December 1, 2006; 92(12): 1732 - 1738. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Dardano, L. Ghiadoni, Y. Plantinga, N. Caraccio, A. Bemi, E. Duranti, S. Taddei, E. Ferrannini, A. Salvetti, and F. Monzani Recombinant Human Thyrotropin Reduces Endothelium-Dependent Vasodilation in Patients Monitored for Differentiated Thyroid Carcinoma J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 4175 - 4178. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Heitzer, V. Rudolph, E. Schwedhelm, M. Karstens, K. Sydow, M. Ortak, P. Tschentscher, T. Meinertz, R. Boger, and S. Baldus Clopidogrel Improves Systemic Endothelial Nitric Oxide Bioavailability in Patients With Coronary Artery Disease: Evidence for Antioxidant and Antiinflammatory Effects Arterioscler Thromb Vasc Biol, July 1, 2006; 26(7): 1648 - 1652. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Vasan Biomarkers of Cardiovascular Disease: Molecular Basis and Practical Considerations Circulation, May 16, 2006; 113(19): 2335 - 2362. [Full Text] [PDF]
|
|
|
|
|
|
G. Bernini, D. Versari, A. Moretti, A. Virdis, L. Ghiadoni, M. Bardini, C. Taurino, D. Canale, S. Taddei, and A. Salvetti Vascular Reactivity in Congenital Hypogonadal Men before and after Testosterone Replacement Therapy J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1691 - 1697. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Forstermann and T. Munzel Endothelial Nitric Oxide Synthase in Vascular Disease: From Marvel to Menace Circulation, April 4, 2006; 113(13): 1708 - 1714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D Tousoulis, M Charakida, and C Stefanadis Endothelial function and inflammation in coronary artery disease Heart, April 1, 2006; 92(4): 441 - 444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Dhaun, J. Goddard, and DavidJ. Webb The Endothelin System and Its Antagonism in Chronic Kidney Disease J. Am. Soc. Nephrol., April 1, 2006; 17(4): 943 - 955. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. N. Bairey Merz, L. J. Shaw, S. E. Reis, V. Bittner, S. F. Kelsey, M. Olson, B. D. Johnson, C. J. Pepine, S. Mankad, B. L. Sharaf, et al. Insights From the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study: Part II: Gender Differences in Presentation, Diagnosis, and Outcome With Regard to Gender-Based Pathophysiology of Atherosclerosis and Macrovascular and Microvascular Coronary Disease J. Am. Coll. Cardiol., February 7, 2006; 47(3_Suppl_S): S21 - S29. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Werner and G. Nickenig Influence of Cardiovascular Risk Factors on Endothelial Progenitor Cells: Limitations for Therapy? Arterioscler Thromb Vasc Biol, February 1, 2006; 26(2): 257 - 266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Guzik, J. Sadowski, B. Guzik, A. Jopek, B. Kapelak, P. Przybylowski, K. Wierzbicki, R. Korbut, D. G. Harrison, and K. M. Channon Coronary Artery Superoxide Production and Nox Isoform Expression in Human Coronary Artery Disease Arterioscler Thromb Vasc Biol, February 1, 2006; 26(2): 333 - 339. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S D Robinson, C A Ludlam, N A Boon, and D E Newby Phosphodiesterase type 5 inhibition does not reverse endothelial dysfunction in patients with coronary heart disease Heart, February 1, 2006; 92(2): 170 - 176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Diez-Marques, M. P. Ruiz-Torres, M. Griera, S. Lopez-Ongil, M. Saura, D. Rodriguez-Puyol, and M. Rodriguez-Puyol Arg-Gly-Asp (RGD)-containing peptides increase soluble guanylate cyclase in contractile cells Cardiovasc Res, February 1, 2006; 69(2): 359 - 369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Werner, S. Wassmann, P. Ahlers, S. Kosiol, and G. Nickenig Circulating CD31+/Annexin V+ Apoptotic Microparticles Correlate With Coronary Endothelial Function in Patients With Coronary Artery Disease Arterioscler Thromb Vasc Biol, January 1, 2006; 26(1): 112 - 116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Al-Benna, C. A. Hamilton, J. D. McClure, P. N. Rogers, G. A. Berg, I. Ford, C. Delles, and A. F. Dominiczak Low-Density Lipoprotein Cholesterol Determines Oxidative Stress and Endothelial Dysfunction in Saphenous Veins From Patients With Coronary Artery Disease Arterioscler Thromb Vasc Biol, January 1, 2006; 26(1): 218 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. L. Mills, H. Tornqvist, S. D. Robinson, M. Gonzalez, K. Darnley, W. MacNee, N. A. Boon, K. Donaldson, A. Blomberg, T. Sandstrom, et al. Diesel Exhaust Inhalation Causes Vascular Dysfunction and Impaired Endogenous Fibrinolysis Circulation, December 20, 2005; 112(25): 3930 - 3936. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Hesse, H. Siedler, S. P. Luntz, B. M. Arendt, R. Goerlich, R. Fricker, M. Heer, and W. E. Haefeli Modulation of endothelial and smooth muscle function by bed rest and hypoenergetic, low-fat nutrition J Appl Physiol, December 1, 2005; 99(6): 2196 - 2203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Pellegrino, G. Storto, P. P. Filardi, A. R. Sorrentino, A. Silvestro, M. Petretta, G. Brevetti, M. Chiariello, M. Salvatore, and A. Cuocolo Relationship Between Brachial Artery Flow-Mediated Dilation and Coronary Flow Reserve in Patients with Peripheral Artery Disease J. Nucl. Med., December 1, 2005; 46(12): 1997 - 2002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Mollnau, M. Oelze, M. August, M. Wendt, A. Daiber, E. Schulz, S. Baldus, A. L. Kleschyov, A. Materne, P. Wenzel, et al. Mechanisms of Increased Vascular Superoxide Production in an Experimental Model of Idiopathic Dilated Cardiomyopathy Arterioscler Thromb Vasc Biol, December 1, 2005; 25(12): 2554 - 2559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Ruano, J. Lopez-Miranda, F. Fuentes, J. A. Moreno, C. Bellido, P. Perez-Martinez, A. Lozano, P. Gomez, Y. Jimenez, and F. Perez Jimenez Phenolic Content of Virgin Olive Oil Improves Ischemic Reactive Hyperemia in Hypercholesterolemic Patients J. Am. Coll. Cardiol., November 15, 2005; 46(10): 1864 - 1868. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Svatikova, R. Wolk, L. O. Lerman, L. A. Juncos, E. L. Greene, J. P. McConnell, and V. K. Somers Oxidative stress in obstructive sleep apnoea Eur. Heart J., November 2, 2005; 26(22): 2435 - 2439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Bendall, N. J. Alp, N. Warrick, S. Cai, D. Adlam, K. Rockett, M. Yokoyama, S. Kawashima, and K. M. Channon Stoichiometric Relationships Between Endothelial Tetrahydrobiopterin, Endothelial NO Synthase (eNOS) Activity, and eNOS Coupling in Vivo: Insights From Transgenic Mice With Endothelial-Targeted GTP Cyclohydrolase 1 and eNOS Overexpression Circ. Res., October 28, 2005; 97(9): 864 - 871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Herman and S. Moncada Therapeutic potential of nitric oxide donors in the prevention and treatment of atherosclerosis Eur. Heart J., October 1, 2005; 26(19): 1945 - 1955. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J A Vita Endothelial function and clinical outcome Heart, October 1, 2005; 91(10): 1278 - 1279. [Full Text] [PDF]
|
|
|
|
|
|
T. Munzel, A. Daiber, and A. Mulsch Explaining the Phenomenon of Nitrate Tolerance Circ. Res., September 30, 2005; 97(7): 618 - 628. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Schnabel, S. Blankenberg, E. Lubos, K. J. Lackner, H. J. Rupprecht, C. Espinola-Klein, N. Jachmann, F. Post, D. Peetz, C. Bickel, et al. Asymmetric Dimethylarginine and the Risk of Cardiovascular Events and Death in Patients With Coronary Artery Disease: Results from the AtheroGene Study Circ. Res., September 2, 2005; 97(5): e53 - e59. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sherwood, A. L. Hinderliter, L. L. Watkins, R. A. Waugh, and J. A. Blumenthal Impaired Endothelial Function in Coronary Heart Disease Patients With Depressive Symptomatology J. Am. Coll. Cardiol., August 16, 2005; 46(4): 656 - 659. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Mellin, M. Isabelle, A. Oudot, C. Vergely-Vandriesse, C. Monteil, B. Di Meglio, J. P. Henry, B. Dautreaux, L. Rochette, C. Thuillez, et al. Transient reduction in myocardial free oxygen radical levels is involved in the improved cardiac function and structure after long-term allopurinol treatment initiated in established chronic heart failure Eur. Heart J., August 1, 2005; 26(15): 1544 - 1550. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Thanyasiri, D. S. Celermajer, and M. R. Adams Endothelial dysfunction occurs in peripheral circulation patients with acute and stable coronary artery disease Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H513 - H517. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sydow, C. E Mondon, and J. P Cooke Insulin resistance: potential role of the endogenous nitric oxide synthase inhibitor ADMA Vascular Medicine, July 1, 2005; 10(1_suppl): S35 - S43. [Abstract] [PDF]
|
|
|
|
|
|
R. H Boger, E. Schwedhelm, R. Maas, S. Quispe-Bravo, and C. Skamira ADMA and oxidative stress may relate to the progression of renal disease: rationale and design of the VIVALDI study Vascular Medicine, July 1, 2005; 10(1_suppl): S97 - S102. [Abstract] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||