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(Circulation. 2003;108:1527.)
© 2003 American Heart Association, Inc.

Review: Clinical Cardiology: New Frontiers

Diabetes and Vascular Disease

Pathophysiology, Clinical Consequences, and Medical Therapy: Part I

Mark A. Creager, MD; Thomas F. Lüscher, MD, FRCP; and prepared with the assistance of Francesco Cosentino, MD, PhD; Joshua A. Beckman, MD

From the Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (M.A.C., J.A.B.); Cardiology, CardioVascular Center, University Hospital and Cardiovascular Research, Institute of Physiology, University Zürich, Switzerland (T.F.L., F.C.); and Cardiology, II Faculty of Medicine, University "La Sapienza", Rome & IRCCS Neuromed, Pozzilli, Italy (F.C.).

Correspondence to Mark A. Creager, MD, Brigham and Women’s Hospital, Cardiovascular Division, 75 Francis St, Boston, MA 02115. E-mail mcreager{at}partners.org

Key Words: diabetes mellitus • cardiovascular diseases • nitric oxide • atherosclerosis • insulin

	Introduction

Top Introduction Pathophysiology of Diabetic... Hyperglycemia and NO Free Fatty Acid Liberation... Insulin Resistance and NO Endothelial Production of... Diabetes and Vascular Smooth... Diabetes, Thrombosis, and... Conclusions References

 
Diabetes mellitus affects approximately 100 million persons worldwide.¹ Five to ten percent have type 1 (formerly known as insulin-dependent) and 90% to 95% have type 2 (non–insulin-dependent) diabetes mellitus. It is likely that the incidence of type 2 diabetes will rise as a consequence of lifestyle patterns contributing to obesity.² Cardiovascular physicians are encountering many of these patients because vascular diseases are the principal causes of death and disability in people with diabetes. The macrovascular manifestations include atherosclerosis and medial calcification. The microvascular consequences, retinopathy and nephropathy, are major causes of blindness and end-stage renal failure. Physicians must be cognizant of the salient features of diabetic vascular disease in order to treat these patients most effectively. The present review will focus on the relationship of diabetes mellitus and atherosclerotic vascular disease, highlighting pathophysiology and molecular mechanisms (Part I) and clinical manifestations and management strategies (Part II).

	Pathophysiology of Diabetic Vascular Disease

Top Introduction Pathophysiology of Diabetic... Hyperglycemia and NO Free Fatty Acid Liberation... Insulin Resistance and NO Endothelial Production of... Diabetes and Vascular Smooth... Diabetes, Thrombosis, and... Conclusions References

 
Abnormalities in endothelial and vascular smooth muscle cell function, as well as a propensity to thrombosis, contribute to atherosclerosis and its complications. Endothelial cells, because of their strategic anatomic position between the circulating blood and the vessel wall, regulate vascular function and structure. In normal endothelial cells, biologically active substances are synthesized and released to maintain vascular homeostasis, ensuring adequate blood flow and nutrient delivery while preventing thrombosis and leukocyte diapedesis.³ Among the important molecules synthesized by the endothelial cell is nitric oxide (NO), which is constitutively produced by endothelial NO synthase (eNOS) through a 5-electron oxidation of the guanidine-nitrogen terminal of L-arginine.⁴ The bioavailability of NO represents a key marker in vascular health. NO causes vasodilation by activating guanylyl cyclase on subjacent vascular smooth muscle cells.⁴ In addition, NO protects the blood vessel from endogenous injury—ie, atherosclerosis—by mediating molecular signals that prevent platelet and leukocyte interaction with the vascular wall and inhibit vascular smooth muscle cell proliferation and migration.^5–7 Conversely, the loss of endothelium-derived NO permits increased activity of the proinflammatory transcription factor nuclear factor kappa B (NF-B), resulting in expression of leukocyte adhesion molecules and production of chemokines and cytokines.⁸ These actions promote monocyte and vascular smooth muscle cell migration into the intima and formation of macrophage foam cells, characterizing the initial morphological changes of atherosclerosis.^8–12 Endothelial dysfunction, as represented by impaired endothelium-dependent, NO-mediated relaxation, occurs in cellular and experimental models of diabetes.^13–16 Similarly, many, but not all, clinical studies have found that endothelium-dependent vasodilation is abnormal in patients with type 1 or type 2 diabetes.^17–20 Thus, decreased levels of NO in diabetes may underlie its atherogenic predisposition.

The bioavailability of NO reflects a balance between its production via NOS and its degradation, particularly by oxygen-derived free radicals.^20–22 Many of the metabolic derangements known to occur in diabetes, including hyperglycemia, excess free fatty acid liberation, and insulin resistance, mediate abnormalities in endothelial cell function by affecting the synthesis or degradation of NO (Figure 2).²³

View larger version (55K): [in this window] [in a new window]   Figure 2. The metabolic abnormalities that characterize diabetes, particularly hyperglycemia, free fatty acids, and insulin resistance, provoke molecular mechanisms that alter the function and structure of blood vessels. These include increased oxidative stress, disturbances of intracellular signal transduction (such as activation of PKC), and activation of RAGE. Consequently, there is decreased availability of NO, increased production of endothelin (ET-1), activation of transcription factors such as NF-B and AP-1, and increased production of prothrombotic factors such as tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1)

	Hyperglycemia and NO

Top Introduction Pathophysiology of Diabetic... Hyperglycemia and NO Free Fatty Acid Liberation... Insulin Resistance and NO Endothelial Production of... Diabetes and Vascular Smooth... Diabetes, Thrombosis, and... Conclusions References

 
The intracellular glucose concentration of endothelial cells mirrors the extracellular environment.²⁴ Experimental evidence supports the notion that hyperglycemia decreases endothelium-derived NO (Figure 1). When normal aortic rings are incubated in a hyperglycemic milieu, endothelium-dependent relaxation is impaired.²⁵ Similarly, endothelium-dependent vasodilation is reduced in healthy subjects during hyperglycemic clamping.²⁶ Hyperglycemia induces a series of cellular events that increase the production of reactive oxygen species (such as superoxide anion) that inactivate NO to form peroxynitrite.^27,28 Hyperglycemia may initiate this process by increasing superoxide anion production via the mitochondrial electron transport chain.²⁸ Superoxide anion then promotes a cascade of endothelial processes that engage increasing numbers of cellular elements to produce oxygen-derived free radicals. For example, superoxide anion activates protein kinase C (PKC),²⁸ or visa versa, activation of PKC may contribute to superoxide generation.^29,30 Activation of PKC by glucose has been implicated in the regulation and activation of membrane-associated NAD(P)H-dependent oxidases and subsequent production of superoxide anion.²⁹ Indeed, the activity of NAD(P)H oxidase and levels of its protein subunits are increased in internal mammary arteries and saphenous veins of patients with diabetes.³¹ Peroxynitrite, resulting from the interaction of NO and superoxide anion, oxidizes the NOS co-factor tetrahydrobiopterin.^32,33 This uncouples the enzyme, which then preferentially increases superoxide anion production over NO production.^34,35 Hence, a cascade effect occurs that results in ever-increasing production of superoxide anion and inactivation of NO.

View larger version (35K): [in this window] [in a new window]   Figure 1. Hyperglycemia and endothelium-derived vasoactive substances. Hyperglycemia decreased the bioavailability of nitric oxide (NO) and prostacyclin (PGI2), and increased the synthesis of vasoconstrictor prostanoids and endothelin (ET-1) via multiple mechanisms, as discussed in the text. PLC indicates phospholipase C; DAG, diacylglycerol; PKC, protein kinase C; eNOS, endothelial nitric oxide synthase; Thr, thrombin; NAD(P)H Ox, nicotinamide adenine dinucleotide phosphate oxidase; O2-, superoxide anion; ONOO-, peroxynitrite; MCP-1, monocyte chemoattractant protein-1; NFß, nuclear factor kappa ß; TNF, tumor necrosis factor; ILs, interleukins; and COX-2, cyclooxygenase-2.

Mitochondrial production of superoxide anion also increases intracellular production of advanced glycation end products (AGEs).²⁸ These glycated proteins adversely affect cellular function both by affecting protein function and by activation of the receptor for AGEs (RAGE).^36,37 AGEs, per se, increase production of oxygen-derived free radicals, and RAGE activation increases intracellular enzymatic superoxide oxide production.^38–40 In addition, increased superoxide anion production activates the hexosamine pathway, which diminishes NOS activation by protein kinase Akt.⁴¹ These processes likely recruit extracellular xanthine oxidase, which further augments the oxidative stress.⁴² Hyperglycemia-induced oxidative stress also may increase levels of asymmetric dimethylarginine, a competitive antagonist of NOS, by impairing the ability of dimethylarginine dimethylaminohydrolase to metabolize asymmetric dimethylarginine.⁴³ The concept that hyperglycemia-induced oxidative stress mediates endothelial dysfunction in patients with diabetes is supported by the observations that intra-arterial infusion of ascorbic acid, a water-soluble antioxidant capable of scavenging superoxide anion,⁴⁴ restores endothelium-dependent vasodilation in healthy subjects exposed to a hyperglycemic clamp and in patients with type 1 or type 2 diabetes.^27,45,46

Hyperglycemia also increases the production of the lipid second messenger diacylglycerol, which causes the membrane translocation and activation of PKC.^47,48 Activation of PKC inhibits the activity of the phosphatidylinositol 3 kinase pathway, thereby limiting activation of Akt kinase and subsequent phosphorylation of NOS, which results in less NO production. Diminished endothelium-dependent relaxation of rabbit aorta exposed to elevated glucose levels is restored by PKC inhibition.²⁵ Administration of a PKC_ß isoform inhibitor to healthy subjects prevents abnormal endothelium-dependent vasodilation caused by hyperglycemia, which confirms the contribution of PKC to endothelial dysfunction.⁴⁹

	Free Fatty Acid Liberation and Endothelial Function

Top Introduction Pathophysiology of Diabetic... Hyperglycemia and NO Free Fatty Acid Liberation... Insulin Resistance and NO Endothelial Production of... Diabetes and Vascular Smooth... Diabetes, Thrombosis, and... Conclusions References

 
Circulating levels of free fatty acids are elevated in diabetes because of their excess liberation from adipose tissue and diminished uptake by skeletal muscle.^50–52 Free fatty acids may impair endothelial function through several mechanisms, including increased production of oxygen-derived free radicals, activation of PKC, and exacerbation of dyslipidemia.^53–55 Infusion of free fatty acids reduces endothelium-dependent vasodilation in animal models and in humans in vivo.⁵⁶ Co-infusion of the antioxidant ascorbic acid improves endothelium-dependent vasodilation in humans treated with free fatty acids, which indicates that oxidative stress mediates the abnormality.⁵⁷ Elevation of free fatty acid concentrations activate PKC and decrease insulin receptor substrate-1–associated phosphatidylinosital-3 kinase activity.^53,58 These effects on signal transduction may decrease NOS activity as discussed above.

The liver responds to free fatty acid flux by increasing very-low-density lipoprotein production and cholesteryl ester synthesis.⁵⁹ This increased production of triglyceride-rich proteins and the diminished clearance by lipoprotein lipase results in hypertriglyceridemia, which is typically observed in diabetes.⁶⁰ Elevated triglyceride concentrations lower HDL by promoting cholesterol transport from HDL to very-low-density lipoprotein.⁵⁹ These abnormalities change LDL morphology, increasing the amount of the more atherogenic, small, dense LDL.^61,62 Both hypertriglyceridemia and low HDL have been associated with endothelial dysfunction.^63,64

	Insulin Resistance and NO

Top Introduction Pathophysiology of Diabetic... Hyperglycemia and NO Free Fatty Acid Liberation... Insulin Resistance and NO Endothelial Production of... Diabetes and Vascular Smooth... Diabetes, Thrombosis, and... Conclusions References

 
Type 2 diabetes mellitus is characterized by insulin resistance. Insulin stimulates NO production from endothelial cells by increasing the activity of NOS via activation of phosphatidylinositol-3 kinase and Akt kinase.^65–67 Thus, in healthy subjects, insulin increases endothelium-dependent (NO-mediated) vasodilation. In insulin-resistant subjects, endothelium-dependent vasodilation is reduced.⁶⁸ Furthermore, insulin-mediated glucose disposal correlates inversely with the severity of the impairment in endothelium-dependent vasodilation.⁶⁹ Drug therapies that increase insulin sensitivity, such as metformin and the thiazolidinediones, improve endothelium-dependent vasodilation.^70,71 Abnormal endothelium-dependent vasodilation in insulin-resistant states may be explained by alterations in intracellular signaling that reduce the production of NO. Specifically, insulin signal transduction via the phosphatidylinositol-3 kinase pathway is impaired, and insulin is less able to activate NOS and produce NO.^53,55,72 Insulin signaling via the mitogen-activated protein kinase pathway remains intact.^55,72 Mitogen-activated protein kinase activation is associated with increased endothelin production and a greater level of inflammation and thrombosis.^73,74

Also, insulin resistance is associated with elevations in free fatty acid levels. Abdominal adipose tissue, the type found prominently in type 2 diabetes, is more insulin resistant and releases more free fatty acids compared with the type of adipose in other locations. Activating lipoprotein lipase to metabolize these free fatty acids increases insulin sensitivity.^75,76 Thus, free fatty acid–induced alterations in intracellular signaling, as discussed previously, may also contribute to decreased NOS activity and reduced production of NO in insulin-resistant states such as type 2 diabetes.

	Endothelial Production of Vasoconstrictors

Top Introduction Pathophysiology of Diabetic... Hyperglycemia and NO Free Fatty Acid Liberation... Insulin Resistance and NO Endothelial Production of... Diabetes and Vascular Smooth... Diabetes, Thrombosis, and... Conclusions References

 
In diabetes, endothelial cell dysfunction is characterized not only by decreased NO but also by increased synthesis of vasoconstrictor prostanoids and endothelin.^77–80 Hyperglycemia increases the expression of cyclooxygenase-2 mRNA and protein levels but not the expression of cyclooxygenase-1 mRNA in cultured human aortic endothelial cells.³⁰ In rabbit arteries exposed to a hyperglycemic milieu in vitro, the production of vasoconstrictor prostanoids is increased, and both cyclooxygenase inhibitors and prostaglandin H₂/thromboxane A₂ receptor antagonists restore endothelium-dependent relaxation.¹³

Endothelin may be particularly relevant to the pathophysiology of vascular disease in diabetes because endothelin promotes inflammation and causes vascular smooth muscle cell contraction and growth.⁸¹ Insulin increases endothelin-1 immunoreactivity in endothelial cells. Also, plasma endothelin-1 concentration increases after administration of insulin to healthy subjects and patients with type 2 diabetes mellitus.^73,74,82,83 In healthy subjects, blockade of endothelin A and B receptors increases forearm blood flow after intra-arterial administration of insulin, which indicates that insulin may affect vascular tone via stimulation of endothelin.⁸⁴ Blockade of endothelin A receptors also increases forearm blood flow in patients with type 2 diabetes mellitus, implicating enhanced activity of endogenous endothelin-1 in resistance vessels of these patients.⁸⁵

	Diabetes and Vascular Smooth Muscle Function

Top Introduction Pathophysiology of Diabetic... Hyperglycemia and NO Free Fatty Acid Liberation... Insulin Resistance and NO Endothelial Production of... Diabetes and Vascular Smooth... Diabetes, Thrombosis, and... Conclusions References

 
The impact of diabetes mellitus on vascular function is not limited to the endothelium. In patients with type 2 diabetes mellitus, the vasodilator response to exogenous NO donors is diminished.¹⁸ Moreover, vasoconstrictor responsiveness to exogenous vasoconstrictors, such as endothelin-1, is reduced.⁸⁶ Dysregulation of vascular smooth muscle function is exacerbated by impairments in sympathetic nervous system function.⁸⁷ Diabetes increases PKC activity, NF-B production, and generation of oxygen-derived free radicals in vascular smooth muscle, akin to these effects in endothelial cells.^55,88 Moreover, diabetes heightens migration of vascular smooth muscle cells into nascent atherosclerotic lesions, where they replicate and produce extracellular matrix—important steps in mature lesion formation.⁸⁹ Vascular smooth muscle cell apoptosis in atherosclerotic lesions is also increased, such that patients with diabetes tend to have fewer smooth muscle cells in the lesions, which increases the propensity for plaque rupture.⁹⁰ In persons with diabetes, elaboration of cytokines diminishes vascular smooth muscle synthesis of collagen and increases production of matrix metalloproteinases, yielding an increased tendency for plaque destabilization and rupture.^91,92

	Diabetes, Thrombosis, and Coagulation

Top Introduction Pathophysiology of Diabetic... Hyperglycemia and NO Free Fatty Acid Liberation... Insulin Resistance and NO Endothelial Production of... Diabetes and Vascular Smooth... Diabetes, Thrombosis, and... Conclusions References

 
Platelet function is abnormal in diabetes as well. Expression of both glycoprotein Ib and IIb/IIIa is increased, augmenting both platelet–von Willebrand factor and platelet–fibrin interaction (Figure 3).⁹³ The intracellular platelet glucose concentration mirrors the extracellular environment and is associated with increased superoxide anion formation and PKC activity and decreased platelet-derived NO.^93,94 Hyperglycemia further changes platelet function by impairing calcium homeostasis and thereby alters aspects of platelet activation and aggregation, including platelet conformation and release of mediators.⁹⁵

View larger version (31K): [in this window] [in a new window]   Figure 3. Platelet function and plasma coagulation factors are altered in diabetes, favoring platelet aggregation and a propensity for thrombosis. There is increased expression of glycoprotein Ib and IIb/IIIa, augmenting both platelet–von Willebrand (vWF) factor and platelet–fibrin interaction. The bioavailability of NO is decreased. Coagulation factors, such as tissue factor, factor VII, and thrombin, are increased; plasminogen activator inhibitor (PAI-1) is increased; and endogenous anticoagulants such as thrombomodulin are decreased.

In diabetes, plasma coagulation factors (eg, factor VII and thrombin) and lesion-based coagulants (eg, tissue factor) are increased, and endogenous anticoagulants (eg, thrombomodulin and protein C) are decreased.^96–98 Also, the production of plasminogen activator inhibitor-1, a fibrinolysis inhibitor, is increased.^{87–90,93,96,99–101} Thus, a propensity for platelet activation and aggregation, coupled with a tendency for coagulation, is relevant to a risk of thrombosis complicating plaque rupture.

	Conclusions

Top Introduction Pathophysiology of Diabetic... Hyperglycemia and NO Free Fatty Acid Liberation... Insulin Resistance and NO Endothelial Production of... Diabetes and Vascular Smooth... Diabetes, Thrombosis, and... Conclusions References

 
Vascular diseases, particularly atherosclerosis, are major causes of disability and death in patients with diabetes mellitus. Diabetes mellitus substantially increases the risk of developing coronary, cerebrovascular, and peripheral arterial disease. The pathophysiology of vascular disease in diabetes involves abnormalities in endothelial, vascular smooth muscle cell, and platelet function. The metabolic abnormalities that characterize diabetes, such as hyperglycemia, increased free fatty acids, and insulin resistance, each provoke molecular mechanisms that contribute to vascular dysfunction. These include decreased bioavailability of NO, increased oxidative stress, disturbances of intracellular signal transduction, and activation of receptors for AGEs. In addition, platelet function is abnormal, and there is increased production of several prothrombotic factors. These abnormalities contribute to the cellular events that cause atherosclerosis and subsequently increase the risk of the adverse cardiovascular events that occur in patients with diabetes and atherosclerosis. A better understanding of the mechanisms leading to vascular dysfunction may unmask new strategies to reduce cardiovascular morbidity and mortality in patients with diabetes.

	Acknowledgments

 
This work is supported by grants from the National Institutes of Health (HL-56607 and HL-04169), the Swiss National Research Foundation (31-68 118.02; 32-67202.01), the Italian Ministry of Health (ICS 030.6/RF00-49), the Swiss Heart Foundation, and the Roche Research Foundation. Dr Creager is the Simon C. Fireman Scholar in Cardiovascular Medicine at Brigham and Women’s Hospital.

	Footnotes

 
This article is part I of a 2-part article. Part II will appear in the September 30, 2003 issue of Circulation.

Dr Creager has served on the scientific advisory boards of Bristol Myers Squibb, KOS, Pfizer, and Sanofi-Synthelabo; and the speakers’ bureau of Merck, Inc; he has received research grants from Bristol Myers Squibb, Eli Lilly, and Pfizer. Dr Lüscher has served as a consultant on clopidogrel for Servier.

	References

Top Introduction Pathophysiology of Diabetic... Hyperglycemia and NO Free Fatty Acid Liberation... Insulin Resistance and NO Endothelial Production of... Diabetes and Vascular Smooth... Diabetes, Thrombosis, and... Conclusions References

 
1. Amos AF, McCarty DJ, Zimmet P. The rising global burden of diabetes and its complications: estimates and projections to the year 2010. Diabet Med. 1997; 14 (suppl 5): S1–S85.[Medline] [Order article via Infotrieve]

2. Mokdad AH, Bowman BA, Ford ES, et al. The continuing epidemics of obesity and diabetes in the United States. JAMA. 2001; 286: 1195–1200.[Abstract/Free Full Text]

3. Kinlay S, Libby P, Ganz P. Endothelial function and coronary artery disease. Curr Opin Lipidol. 2001; 12: 383–389.[CrossRef][Medline] [Order article via Infotrieve]

4. Moncada S, Higgs A. The L-arginine–nitric oxide pathway. N Engl J Med. 1993; 329: 2002–2012.[Free Full Text]

5. Radomski MW, Palmer RM, Moncada S. The role of nitric oxide and cGMP in platelet adhesion to vascular endothelium. Biochem Biophys Res Commun. 1987; 148: 1482–1489.[CrossRef][Medline] [Order article via Infotrieve]

6. Sarkar R, Meinberg EG, Stanley JC, et al. Nitric oxide reversibly inhibits the migration of cultured vascular smooth muscle cells. Circ Res. 1996; 78: 225–230.[Abstract/Free Full Text]

7. Kubes P, Suzuki M, Granger DN. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci U S A. 1991; 88: 4651–4655.[Abstract/Free Full Text]

8. Zeiher AM, Fisslthaler B, Schray-Utz B, et al. Nitric oxide modulates the expression of monocyte chemoattractant protein 1 in cultured human endothelial cells. Circ Res. 1995; 76: 980–986.[Abstract/Free Full Text]

9. Libby P. Changing concepts of atherogenesis. J Intern Med. 2000; 247: 349–358.[CrossRef][Medline] [Order article via Infotrieve]

10. Nomura S, Shouzu A, Omoto S, et al. Significance of chemokines and activated platelets in patients with diabetes. Clin Exp Immunol. 2000; 121: 437–443.[CrossRef][Medline] [Order article via Infotrieve]

11. Mohamed AK, Bierhaus A, Schiekofer S, et al. The role of oxidative stress and NF-kappaB activation in late diabetic complications. Biofactors. 1999; 10: 157–167.[Medline] [Order article via Infotrieve]

12. Collins T, Cybulsky MI. NF-kappaB: pivotal mediator or innocent bystander in atherogenesis? J Clin Invest. 2001; 107: 255–264.[Medline] [Order article via Infotrieve]

13. Tesfamariam B, Brown ML, Deykin D, et al. Elevated glucose promotes generation of endothelium-derived vasoconstrictor prostanoids in rabbit aorta. J Clin Invest. 1990; 85: 929–932.[Medline] [Order article via Infotrieve]

14. Bohlen HG, Lash JM. Topical hyperglycemia rapidly suppresses EDRF-mediated vasodilation of normal rat arterioles. Am J Physiol. 1993; 265: H219–H225.[Medline] [Order article via Infotrieve]

15. Meraji S, Jayakody L, Senaratne MP, et al. Endothelium-dependent relaxation in aorta of BB rat. Diabetes. 1987; 36: 978–981.[Abstract]

16. Pieper GM, Meier DA, Hager SR. Endothelial dysfunction in a model of hyperglycemia and hyperinsulinemia. Am J Physiol. 1995; 269: H845–H850.[Medline] [Order article via Infotrieve]

17. Johnstone MT, Creager SJ, Scales KM, et al. Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. Circulation. 1993; 88: 2510–2516.[Abstract/Free Full Text]

18. Williams SB, Cusco JA, Roddy MA, et al. Impaired nitric oxide–mediated vasodilation in patients with non–insulin-dependent diabetes mellitus. J Am Coll Cardiol. 1996; 27: 567–574.[Abstract]

19. Clarkson P, Celermajer DS, Donald AE, et al. Impaired vascular reactivity in insulin-dependent diabetes mellitus is related to disease duration and low density lipoprotein cholesterol levels. J Am Coll Cardiol. 1996; 28: 573–579.[Abstract]

20. McVeigh GE, Brennan GM, Johnston GD, et al. Impaired endothelium-dependent and independent vasodilation in patients with type 2 (non–insulin-dependent) diabetes mellitus. Diabetologia. 1992; 35: 771–776.[Medline] [Order article via Infotrieve]

21. Arnal JF, Dinh-Xuan AT, Pueyo M, et al. Endothelium-derived nitric oxide and vascular physiology and pathology. Cell Mol Life Sci. 1999; 55: 1078–1087.[CrossRef][Medline] [Order article via Infotrieve]

22. Cosentino F, Hishikawa K, Katusic ZS, et al. High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells. Circulation. 1997; 96: 25–28.[Abstract/Free Full Text]

23. King GL. The role of hyperglycaemia and hyperinsulinaemia in causing vascular dysfunction in diabetes. Ann Med. 1996; 28: 427–432.[Medline] [Order article via Infotrieve]

24. Kaiser N, Sasson S, Feener EP, et al. Differential regulation of glucose transport and transporters by glucose in vascular endothelial and smooth muscle cells. Diabetes. 1993; 42: 80–89.[Abstract]

25. Tesfamariam B, Brown ML, Cohen RA. Elevated glucose impairs endothelium-dependent relaxation by activating protein kinase C. J Clin Invest. 1991; 87: 1643–1648.[Medline] [Order article via Infotrieve]

26. Williams SB, Goldfine AB, Timimi FK, et al. Acute hyperglycemia attenuates endothelium-dependent vasodilation in humans in vivo. Circulation. 1998; 97: 1695–1701.[Abstract/Free Full Text]

27. Beckman JA, Goldfine AB, Gordon MB, et al. Ascorbate restores endothelium-dependent vasodilation impaired by acute hyperglycemia in humans. Circulation. 2001; 103: 1618–1623.[Abstract/Free Full Text]

28. Nishikawa T, Edelstein D, Du XL, et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature. 2000; 404: 787–790.[CrossRef][Medline] [Order article via Infotrieve]

29. Hink U, Li H, Mollnau H, et al. Mechanisms underlying endothelial dysfunction in diabetes mellitus. Circ Res. 2001; 88: E14–E22.[Medline] [Order article via Infotrieve]

30. Cosentino F, Eto M, De Paolis P, et al. High glucose causes upregulation of cyclooxygenase-2 and alters prostanoid profile in human endothelial cells: role of protein kinase C and reactive oxygen species. Circulation. 2003; 107: 1017–1023.[Abstract/Free Full Text]

31. Guzik TJ, Mussa S, Gastaldi D, et al. Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase. Circulation. 2002; 105: 1656–1662.[Abstract/Free Full Text]

32. Koppenol WH, Moreno JJ, Pryor WA, et al. Peroxynitrite, a cloaked oxidant formed by nitric oxide and superoxide. Chem Res Toxicol. 1992; 5: 834–842.[CrossRef][Medline] [Order article via Infotrieve]

33. Laursen JB, Somers M, Kurz S, et al. Endothelial regulation of vasomotion in apoE-deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterin. Circulation. 2001; 103: 1282–1288.[Abstract/Free Full Text]

34. Milstien S, Katusic Z. Oxidation of tetrahydrobiopterin by peroxynitrite: implications for vascular endothelial function. Biochem Biophys Res Comm. 1999; 263: 681–684.[CrossRef][Medline] [Order article via Infotrieve]

35. Wever RM, Luscher TF, Cosentino F, et al. Atherosclerosis and the two faces of endothelial nitric oxide synthase. Circulation. 1998; 97: 108–112.[Free Full Text]

36. Schmidt AM, Yan SD, Wautier JL, et al. Activation of receptor for advanced glycation end products: a mechanism for chronic vascular dysfunction in diabetic vasculopathy and atherosclerosis. Circ Res. 1999; 84: 489–497.[Abstract/Free Full Text]

37. Schmidt AM, Hori O, Brett J, et al. Cellular receptors for advanced glycation end products: implications for induction of oxidant stress and cellular dysfunction in the pathogenesis of vascular lesions. Arterioscler Thromb. 1994; 14: 1521–1528.[Abstract/Free Full Text]

38. Schmidt AM, Stern D. Atherosclerosis and diabetes: the RAGE connection. Curr Atheroscler Rep. 2000; 2: 430–436.[Medline] [Order article via Infotrieve]

39. Tan KC, Chow WS, Ai VH, et al. Advanced glycation end products and endothelial dysfunction in type 2 diabetes. Diabetes Care. 2002; 25: 1055–1059.[Abstract/Free Full Text]

40. Wautier MP, Chappey O, Corda S, et al. Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE. Am J Physiol Endocrinol Metab. 2001; 280: E685–E694.[Abstract/Free Full Text]

41. Du XL, Edelstein D, Dimmeler S, et al. Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site. J Clin Invest. 2001; 108: 1341–1348.[CrossRef][Medline] [Order article via Infotrieve]

42. Desco MC, Asensi M, Marquez R, et al. Xanthine oxidase is involved in free radical production in type 1 diabetes: protection by allopurinol. Diabetes. 2002; 51: 1118–11124.[Abstract/Free Full Text]

43. Lin KY, Ito A, Asagami T, et al. Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase. Circulation. 2002; 106: 987–992.[Abstract/Free Full Text]

44. 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.[Abstract/Free Full Text]

45. Timimi FK, Ting HH, Haley EA, et al. Vitamin C improves endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. J Am Coll Cardiol. 1998; 31: 552–557.[Abstract/Free Full Text]

46. Ting HH, Timimi FK, Boles KS, et al. Vitamin C improves endothelium-dependent vasodilation in patients with non–insulin-dependent diabetes mellitus. J Clin Invest. 1996; 97: 22–28.[Medline] [Order article via Infotrieve]

47. Xia P, Inoguchi T, Kern TS, et al. Characterization of the mechanism for the chronic activation of diacylglycerol–protein kinase C pathway in diabetes and hypergalactosemia. Diabetes. 1994; 43: 1122–1129.[Abstract]

48. Inoguchi T, Xia P, Kunisaki M, et al. Insulin’s effect on protein kinase C and diacylglycerol induced by diabetes and glucose in vascular tissues. Am J Physiol. 1994; 267: E369–E379.[Medline] [Order article via Infotrieve]

49. Beckman JA, Goldfine AB, Gordon MB, et al. Inhibition of protein kinase C beta prevents impaired endothelium-dependent vasodilation caused by hyperglycemia in humans. Circ Res. 2002; 90: 107–111.[Abstract/Free Full Text]

50. Boden G. Free fatty acids, insulin resistance, and type 2 diabetes mellitus. Proc Assoc Am Physicians. 1999; 111: 241–248.[CrossRef][Medline] [Order article via Infotrieve]

51. Fujimoto WY. The importance of insulin resistance in the pathogenesis of type 2 diabetes mellitus. Am J Med. 2000; 108 (suppl 6a): 9S–14S.[Medline] [Order article via Infotrieve]

52. Kelley DE, Simoneau JA. Impaired free fatty acid utilization by skeletal muscle in non–insulin-dependent diabetes mellitus. J Clin Invest. 1994; 94: 2349–2356.[Medline] [Order article via Infotrieve]

53. Dresner A, Laurent D, Marcucci M, et al. Effects of free fatty acids on glucose transport and IRS-1–associated phosphatidylinositol 3-kinase activity. J Clin Invest. 1999; 103: 253–259.[Medline] [Order article via Infotrieve]

54. Dichtl W, Nilsson L, Goncalves I, et al. Very low-density lipoprotein activates nuclear factor-kappaB in endothelial cells. Circ Res. 1999; 84: 1085–1094.[Abstract/Free Full Text]

55. Inoguchi T, Li P, Umeda F, et al. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C–dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes. 2000; 49: 1939–1945.[Abstract]

56. Steinberg HO, Tarshoby M, Monestel R, et al. Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation. J Clin Invest. 1997; 100: 1230–1239.[Medline] [Order article via Infotrieve]

57. Pleiner J, Schaller G, Mittermayer F, et al. FFA-induced endothelial dysfunction can be corrected by vitamin C. J Clin Endocrinol Metab. 2002; 87: 2913–2917.[Abstract/Free Full Text]

58. Griffin ME, Marcucci MJ, Cline GW, et al. Free fatty acid–induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade. Diabetes. 1999; 48: 1270–1274.[Abstract]

59. Sniderman AD, Scantlebury T, Cianflone K. Hypertriglyceridemic hyperapob: the unappreciated atherogenic dyslipoproteinemia in type 2 diabetes mellitus. Ann Intern Med. 2001; 135: 447–459.[Abstract/Free Full Text]

60. Cummings MH, Watts GF, Umpleby AM, et al. Increased hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 in NIDDM. Diabetologia. 1995; 38: 959–967.[Medline] [Order article via Infotrieve]

61. Sniderman A, Thomas D, Marpole D, et al. Low density lipoprotein: a metabolic pathway for return of cholesterol to the splanchnic bed. J Clin Invest. 1978; 61: 867–873.[Medline] [Order article via Infotrieve]

62. Dimitriadis E, Griffin M, Owens D, et al. Oxidation of low-density lipoprotein in NIDDM: its relationship to fatty acid composition. Diabetologia. 1995; 38: 1300–1306.[Medline] [Order article via Infotrieve]

63. de Man FH, Weverling-Rijnsburger AW, van der Laarse A, et al. Not acute but chronic hypertriglyceridemia is associated with impaired endothelium-dependent vasodilation: reversal after lipid-lowering therapy by atorvastatin. Arterioscler Thromb Vasc Biol. 2000; 20: 744–750.[Abstract/Free Full Text]

64. Kuhn FE, Mohler ER, Satler LF, et al. Effects of high-density lipoprotein on acetylcholine-induced coronary vasoreactivity. Am J Cardiol. 1991; 68: 1425–1430.[CrossRef][Medline] [Order article via Infotrieve]

65. Zeng G, Quon MJ. Insulin-stimulated production of nitric oxide is inhibited by wortmannin: direct measurement in vascular endothelial cells. J Clin Invest. 1996; 98: 894–898.[Medline] [Order article via Infotrieve]

66. Kuboki K, Jiang ZY, Takahara N, et al. Regulation of endothelial constitutive nitric oxide synthase gene expression in endothelial cells and in vivo: a specific vascular action of insulin. Circulation. 2000; 101: 676–681.[Abstract/Free Full Text]

67. Zeng G, Nystrom FH, Ravichandran LV, et al. Roles for insulin receptor, PI3-kinase, and Akt in insulin-signaling pathways related to production of nitric oxide in human vascular endothelial cells. Circulation. 2000; 101: 1539–1545.[Abstract/Free Full Text]

68. Laakso M, Edelman SV, Brechtel G, et al. Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man: a novel mechanism for insulin resistance. J Clin Invest. 1990; 85: 1844–1852.[Medline] [Order article via Infotrieve]

69. Mather K, Laakso M, Edelman S, et al. Evidence for physiological coupling of insulin-mediated glucose metabolism and limb blood flow. Am J Physiol Endocrinol Metab. 2000; 279: E1264–E1270.[Abstract/Free Full Text]

70. Mather KJ, Verma S, Anderson TJ. Improved endothelial function with metformin in type 2 diabetes mellitus. J Am Coll Cardiol. 2001; 37: 1344–1350.[Abstract/Free Full Text]

71. Watanabe Y, Sunayama S, Shimada K, et al. Troglitazone improves endothelial dysfunction in patients with insulin resistance. J Atheroscler Thromb. 2000; 7: 159–163.[Medline] [Order article via Infotrieve]

72. Montagnani M, Golovchenko I, Kim I, et al. Inhibition of phosphatidylinositol 3-kinase enhances mitogenic actions of insulin in endothelial cells. J Biol Chem. 2002; 277: 1794–1799.[Abstract/Free Full Text]

73. Oliver FJ, de la Rubia G, Feener EP, et al. Stimulation of endothelin-1 gene expression by insulin in endothelial cells. J Biol Chem. 1991; 266: 23251–23256.[Abstract/Free Full Text]

74. Ferri C, Pittoni V, Piccoli A, et al. Insulin stimulates endothelin-1 secretion from human endothelial cells and modulates its circulating levels in vivo. J Clin Endocrinol Metab. 1995; 80: 829–835.[Abstract]

75. de Souza CJ, Eckhardt M, Gagen K, et al. Effects of pioglitazone on adipose tissue remodeling within the setting of obesity and insulin resistance. Diabetes. 2001; 50: 1863–1871.[Abstract/Free Full Text]

76. Kusunoki M, Hara T, Tsutsumi K, et al. The lipoprotein lipase activator, NO-1886, suppresses fat accumulation and insulin resistance in rats fed a high-fat diet. Diabetologia. 2000; 43: 875–880.[CrossRef][Medline] [Order article via Infotrieve]

77. De Vriese AS, Verbeuren TJ, Van de Voorde J, et al. Endothelial dysfunction in diabetes. Br J Pharmacol. 2000; 130: 963–974.[CrossRef][Medline] [Order article via Infotrieve]

78. Luft FC. Proinflammatory effects of angiotensin II and endothelin: targets for progression of cardiovascular and renal diseases. Curr Opin Nephrol Hypertens. 2002; 11: 59–66.[CrossRef][Medline] [Order article via Infotrieve]

79. Golovchenko I, Goalstone ML, Watson P, et al. Hyperinsulinemia enhances transcriptional activity of nuclear factor-kappaB induced by angiotensin II, hyperglycemia, and advanced glycosylation end products in vascular smooth muscle cells. Circ Res. 2000; 87: 746–752.[Abstract/Free Full Text]

80. O’Driscoll G, Green D, Rankin J, et al. Improvement in endothelial function by angiotensin converting enzyme inhibition in insulin-dependent diabetes mellitus. J Clin Invest. 1997; 100: 678–684.[Medline] [Order article via Infotrieve]

81. Hopfner RL, Gopalakrishnan V. Endothelin: emerging role in diabetic vascular complications. Diabetologia. 1999; 42: 1383–1394.[CrossRef][Medline] [Order article via Infotrieve]

82. Piatti PM, Monti LD, Conti M, et al. Hypertriglyceridemia and hyperinsulinemia are potent inducers of endothelin-1 release in humans. Diabetes. 1996; 45: 316–321.[Abstract]

83. Wolpert HA, Steen SN, Istfan NW, et al. Insulin modulates circulating endothelin-1 levels in humans. Metabolism. 1993; 42: 1027–1030.[CrossRef][Medline] [Order article via Infotrieve]

84. Cardillo C, Nambi SS, Kilcoyne CM, et al. Insulin stimulates both endothelin and nitric oxide activity in the human forearm. Circulation. 1999; 100: 820–825.[Abstract/Free Full Text]

85. Cardillo C, Campia U, Bryant MB, et al. Increased activity of endogenous endothelin in patients with type II diabetes mellitus. Circulation. 2002; 106: 1783–1787.[Abstract/Free Full Text]

86. Nugent AG, McGurk C, Hayes JR, et al. Impaired vasoconstriction to endothelin 1 in patients with NIDDM. Diabetes. 1996; 45: 105–107.[Abstract]

87. McDaid EA, Monaghan B, Parker AI, et al. Peripheral autonomic impairment in patients newly diagnosed with type II diabetes. Diabetes Care. 1994; 17: 1422–1427.[Abstract]

88. Hattori Y, Hattori S, Sato N, et al. High-glucose-induced nuclear factor kappaB activation in vascular smooth muscle cells. Cardiovasc Res. 2000; 46: 188–197.[Abstract/Free Full Text]

89. Suzuki LA, Poot M, Gerrity RG, et al. Diabetes accelerates smooth muscle accumulation in lesions of atherosclerosis: lack of direct growth-promoting effects of high glucose levels. Diabetes. 2001; 50: 851–860.[Abstract/Free Full Text]

90. Fukumoto H, Naito Z, Asano G, et al. Immunohistochemical and morphometric evaluations of coronary atherosclerotic plaques associated with myocardial infarction and diabetes mellitus. J Atheroscler Thromb. 1998; 5: 29–35.[Medline] [Order article via Infotrieve]

91. Hussain MJ, Peakman M, Gallati H, et al. Elevated serum levels of macrophage-derived cytokines precede and accompany the onset of IDDM. Diabetologia. 1996; 39: 60–69.[Medline] [Order article via Infotrieve]

92. Uemura S, Matsushita H, Li W, et al. Diabetes mellitus enhances vascular matrix metalloproteinase activity: role of oxidative stress. Circ Res. 2001; 88: 1291–1298.[Abstract/Free Full Text]

93. Vinik AI, Erbas T, Park TS, et al. Platelet dysfunction in type 2 diabetes. Diabetes Care. 2001; 24: 1476–1485.[Abstract/Free Full Text]

94. Assert R, Scherk G, Bumbure A, et al. Regulation of protein kinase C by short term hyperglycaemia in human platelets in vivo and in vitro. Diabetologia. 2001; 44: 188–195.[CrossRef][Medline] [Order article via Infotrieve]

95. Li Y, Woo V, Bose R. Platelet hyperactivity and abnormal Ca(2+) homeostasis in diabetes mellitus. Am J Physiol Heart Circ Physiol. 2001; 280: H1480–H1489.[Abstract/Free Full Text]

96. Hafer-Macko CE, Ivey FM, Gyure KA, et al. Thrombomodulin deficiency in human diabetic nerve microvasculature. Diabetes. 2002; 51: 1957–1963.[Abstract/Free Full Text]

97. Ceriello A, Giacomello R, Stel G, et al. Hyperglycemia-induced thrombin formation in diabetes: the possible role of oxidative stress. Diabetes. 1995; 44: 924–928.[Abstract]

98. Ceriello A, Giugliano D, Quatraro A, et al. Evidence for a hyperglycaemia-dependent decrease of antithrombin III–thrombin complex formation in humans. Diabetologia. 1990; 33: 163–167.[CrossRef][Medline] [Order article via Infotrieve]

99. Ren S, Lee H, Hu L, et al. Impact of diabetes-associated lipoproteins on generation of fibrinolytic regulators from vascular endothelial cells. J Clin Endocrinol Metab. 2002; 87: 286–291.[Abstract/Free Full Text]

100. Kario K, Matsuo T, Kobayashi H, et al. Activation of tissue factor–induced coagulation and endothelial cell dysfunction in non–insulin-dependent diabetic patients with microalbuminuria. Arterioscler Thromb Vasc Biol. 1995; 15: 1114–1120.[Abstract/Free Full Text]

101. Pandolfi A, Cetrullo D, Polishuck R, et al. Plasminogen activator inhibitor type 1 is increased in the arterial wall of type II diabetic subjects. Arterioscler Thromb Vasc Biol. 2001; 21: 1378–1382.[Abstract/Free Full Text]

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				A. R. Albers, M. Z. Krichavsky, and G. J. Balady Stress Testing in Patients With Diabetes Mellitus: Diagnostic and Prognostic Value Circulation, January 31, 2006; 113(4): 583 - 592. [Full Text] [PDF]

				M. W Clarke, N. C Ward, J. H. Wu, J. M Hodgson, I. B Puddey, and K. D Croft Supplementation with mixed tocopherols increases serum and blood cell {gamma}-tocopherol but does not alter biomarkers of platelet activation in subjects with type 2 diabetes Am. J. Clinical Nutrition, January 1, 2006; 83(1): 95 - 102. [Abstract] [Full Text] [PDF]

				P. M. Thule, A. G. Campbell, D. J. Kleinhenz, D. E. Olson, J. J. Boutwell, R. L. Sutliff, and C. M. Hart Hepatic insulin gene therapy prevents deterioration of vascular function and improves adipocytokine profile in STZ-diabetic rats Am J Physiol Endocrinol Metab, January 1, 2006; 290(1): E114 - E122. [Abstract] [Full Text] [PDF]

				M. Aragno, R. Mastrocola, C. Medana, F. Restivo, M. G. Catalano, N. Pons, O. Danni, and G. Boccuzzi Up-Regulation of Advanced Glycated Products Receptors in the Brain of Diabetic Rats Is Prevented by Antioxidant Treatment Endocrinology, December 1, 2005; 146(12): 5561 - 5567. [Abstract] [Full Text] [PDF]

				J.-Z. Sheng, D. Wang, and A. P. Braun DAF-FM (4-Amino-5-methylamino-2',7'-difluorofluorescein) Diacetate Detects Impairment of Agonist-Stimulated Nitric Oxide Synthesis by Elevated Glucose in Human Vascular Endothelial Cells: Reversal by Vitamin C and L-Sepiapterin J. Pharmacol. Exp. Ther., November 1, 2005; 315(2): 931 - 940. [Abstract] [Full Text] [PDF]

				A. H. Bubolz, H. Li, Q. Wu, and Y. Liu Enhanced oxidative stress impairs cAMP-mediated dilation by reducing Kv channel function in small coronary arteries of diabetic rats Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H1873 - H1880. [Abstract] [Full Text] [PDF]

				X. Jouven, R. N. Lemaitre, T. D. Rea, N. Sotoodehnia, J.-P. Empana, and D. S. Siscovick Diabetes, glucose level, and risk of sudden cardiac death Eur. Heart J., October 2, 2005; 26(20): 2142 - 2147. [Abstract] [Full Text] [PDF]

				J.-P. Collet and G. Montalescot The acute reperfusion management of STEMI in patients with impaired glucose tolerance and type 2 diabetes Diabetes and Vascular Disease Research, October 1, 2005; 2(3): 136 - 143. [Abstract] [PDF]

				M. Bartnik, K. Malmberg, and L. Ryden Management of patients with type 2 diabetes after acute coronary syndromes Diabetes and Vascular Disease Research, October 1, 2005; 2(3): 144 - 154. [Abstract] [PDF]

				H Tamura, J Kiryu, K Miyamoto, K Nishijima, H Katsuta, S Miyahara, F Hirose, Y Honda, and N Yoshimura In vivo evaluation of ocular inflammatory responses in experimental diabetes Br J Ophthalmol, August 1, 2005; 89(8): 1052 - 1057. [Abstract] [Full Text] [PDF]

				C. A. Daly, K. M. Fox, W. J. Remme, M. E. Bertrand, R. Ferrari, M. L. Simoons, and on behalf of the EUROPA investigators The effect of perindopril on cardiovascular morbidity and mortality in patients with diabetes in the EUROPA study: results from the PERSUADE substudy Eur. Heart J., July 2, 2005; 26(14): 1369 - 1378. [Abstract] [Full Text] [PDF]

				E. D. Beishuizen, J. T. Tamsma, J. W. Jukema, M. A. van de Ree, J. C. M. van der Vijver, A. E. Meinders, and M. V. Huisman The Effect of Statin Therapy on Endothelial Function in Type 2 Diabetes Without Manifest Cardiovascular Disease Diabetes Care, July 1, 2005; 28(7): 1668 - 1674. [Abstract] [Full Text] [PDF]

				P. L. Huang Unraveling the Links Between Diabetes, Obesity, and Cardiovascular Disease Circ. Res., June 10, 2005; 96(11): 1129 - 1131. [Full Text] [PDF]

				J. Molnar, S. Yu, N. Mzhavia, C. Pau, I. Chereshnev, and H. M. Dansky Diabetes Induces Endothelial Dysfunction but Does Not Increase Neointimal Formation in High-Fat Diet Fed C57BL/6J Mice Circ. Res., June 10, 2005; 96(11): 1178 - 1184. [Abstract] [Full Text] [PDF]

				M. S. O'Neill, A. Veves, A. Zanobetti, J. A. Sarnat, D. R. Gold, P. A. Economides, E. S. Horton, and J. Schwartz Diabetes Enhances Vulnerability to Particulate Air Pollution-Associated Impairment in Vascular Reactivity and Endothelial Function Circulation, June 7, 2005; 111(22): 2913 - 2920. [Abstract] [Full Text] [PDF]

				J. O. Prior, M. J. Quinones, M. Hernandez-Pampaloni, A. D. Facta, T. H. Schindler, J. W. Sayre, W. A. Hsueh, and H. R. Schelbert Coronary Circulatory Dysfunction in Insulin Resistance, Impaired Glucose Tolerance, and Type 2 Diabetes Mellitus Circulation, May 10, 2005; 111(18): 2291 - 2298. [Abstract] [Full Text] [PDF]

				I. Iakovou, T. Schmidt, E. Bonizzoni, L. Ge, G. M. Sangiorgi, G. Stankovic, F. Airoldi, A. Chieffo, M. Montorfano, M. Carlino, et al. Incidence, Predictors, and Outcome of Thrombosis After Successful Implantation of Drug-Eluting Stents JAMA, May 4, 2005; 293(17): 2126 - 2130. [Abstract] [Full Text] [PDF]

				Z. T. Bloomgarden The European Association for the Study of Diabetes Diabetes Care, May 1, 2005; 28(5): 1250 - 1257. [Full Text] [PDF]

				J. D. Flaherty and C. J. Davidson Diabetes and Coronary Revascularization JAMA, March 23, 2005; 293(12): 1501 - 1508. [Abstract] [Full Text] [PDF]

				K. V. Ramana, B. Friedrich, R. Tammali, M. B. West, A. Bhatnagar, and S. K. Srivastava Requirement of Aldose Reductase for the Hyperglycemic Activation of Protein Kinase C and Formation of Diacylglycerol in Vascular Smooth Muscle Cells Diabetes, March 1, 2005; 54(3): 818 - 829. [Abstract] [Full Text] [PDF]

				M. L. Sheu, F. M. Ho, R. S. Yang, K. F. Chao, W. W. Lin, S. Y. Lin-Shiau, and S.-H. Liu High Glucose Induces Human Endothelial Cell Apoptosis Through a Phosphoinositide 3-Kinase-Regulated Cyclooxygenase-2 Pathway Arterioscler Thromb Vasc Biol, March 1, 2005; 25(3): 539 - 545. [Abstract] [Full Text] [PDF]

				S. Cai, J. Khoo, and K. M. Channon Augmented BH4 by gene transfer restores nitric oxide synthase function in hyperglycemic human endothelial cells Cardiovasc Res, March 1, 2005; 65(4): 823 - 831. [Abstract] [Full Text] [PDF]

				A. V. Finn, I. F. Palacios, A. Kastrati, and H. K. Gold Drug-eluting stents for diabetes mellitus: A rush to judgment? J. Am. Coll. Cardiol., February 15, 2005; 45(4): 479 - 483. [Abstract] [Full Text] [PDF]

				A. Prasad, G. W. Stone, T. D. Stuckey, C. O. Costantini, P. J. Zimetbaum, M. McLaughlin, R. Mehran, E. Garcia, J. E. Tcheng, D. A. Cox, et al. Impact of diabetes mellitus on myocardial perfusion after primary angioplasty in patients with acute myocardial infarction J. Am. Coll. Cardiol., February 15, 2005; 45(4): 508 - 514. [Abstract] [Full Text] [PDF]

				A. Tajaddini, D. L. Kilpatrick, P. Schoenhagen, E. M. Tuzcu, M. Lieber, and D. G. Vince Impact of age and hyperglycemia on the mechanical behavior of intact human coronary arteries: an ex vivo intravascular ultrasound study Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H250 - H255. [Abstract] [Full Text] [PDF]

				P. R. Moreno and V. Fuster New aspects in the pathogenesis of diabetic atherothrombosis J. Am. Coll. Cardiol., December 21, 2004; 44(12): 2293 - 2300. [Abstract] [Full Text] [PDF]

				K. K. Koh, M. J. Quon, S. H. Han, W.-J. Chung, J. Y. Ahn, Y.-H. Seo, M. H. Kang, T. H. Ahn, I. S. Choi, and E. K. Shin Additive Beneficial Effects of Losartan Combined With Simvastatin in the Treatment of Hypercholesterolemic, Hypertensive Patients Circulation, December 14, 2004; 110(24): 3687 - 3692. [Abstract] [Full Text] [PDF]

				D. J Collinson, R. Rea, and R. Donnelly Masterclass series in peripheral arterial disease: Vascular risk: diabetes Vascular Medicine, November 1, 2004; 9(4): 307 - 310. [PDF]

				T. Hamanishi, H. Furuta, H. Kato, A. Doi, M. Tamai, H. Shimomura, S. Sakagashira, M. Nishi, H. Sasaki, T. Sanke, et al. Functional Variants in the Glutathione Peroxidase-1 (GPx-1) Gene Are Associated With Increased Intima-Media Thickness of Carotid Arteries and Risk of Macrovascular Diseases in Japanese Type 2 Diabetic Patients Diabetes, September 1, 2004; 53(9): 2455 - 2460. [Abstract] [Full Text] [PDF]

				J. Li, Z. Ma, Z.-L. Tang, T. Stevens, B. Pitt, and S. Li CpG DNA-mediated immune response in pulmonary endothelial cells Am J Physiol Lung Cell Mol Physiol, September 1, 2004; 287(3): L552 - L558. [Abstract] [Full Text] [PDF]

				A. Kouroedov, M. Eto, H. Joch, M. Volpe, T. F. Luscher, and F. Cosentino Selective Inhibition of Protein Kinase C{beta}2 Prevents Acute Effects of High Glucose on Vascular Cell Adhesion Molecule-1 Expression in Human Endothelial Cells Circulation, July 6, 2004; 110(1): 91 - 96. [Abstract] [Full Text] [PDF]

				G. E. Sonnenberg, G. R. Krakower, L. J. Martin, M. Olivier, A. E. Kwitek, A. G. Comuzzie, J. Blangero, and A. H. Kissebah Genetic determinants of obesity-related lipid traits J. Lipid Res., April 1, 2004; 45(4): 610 - 615. [Abstract] [Full Text] [PDF]

				S. V. Brodsky, O. Gealekman, J. Chen, F. Zhang, N. Togashi, M. Crabtree, S. S. Gross, A. Nasjletti, and M. S. Goligorsky Prevention and Reversal of Premature Endothelial Cell Senescence and Vasculopathy in Obesity-Induced Diabetes by Ebselen Circ. Res., February 20, 2004; 94(3): 377 - 384. [Abstract] [Full Text] [PDF]

				M. Zeller, Y. Cottin, M.-C. Brindisi, G. Dentan, Y. Laurent, L. Janin-Manificat, I. L'Huillier, J.-C. Beer, C. Touzery, H. Makki, et al. Impaired fasting glucose and cardiogenic shock in patients with acute myocardial infarction Eur. Heart J., February 2, 2004; 25(4): 308 - 312. [Abstract] [Full Text] [PDF]

				M. Roffi and E. J. Topol Percutaneous coronary intervention in diabetic patients with non-ST-segment elevation acute coronary syndromes Eur. Heart J., February 1, 2004; 25(3): 190 - 198. [Abstract] [Full Text] [PDF]

				P. C. Deedwania Metabolic Syndrome and Vascular Disease: Is Nature or Nurture Leading the New Epidemic of Cardiovascular Disease? Circulation, January 6, 2004; 109(1): 2 - 4. [Full Text] [PDF]

				T. F. Luscher, M. A. Creager, J. A. Beckman, and F. Cosentino Diabetes and Vascular Disease: Pathophysiology, Clinical Consequences, and Medical Therapy: Part II Circulation, September 30, 2003; 108(13): 1655 - 1661. [Full Text] [PDF]

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