(Circulation. 1996;93:1334-1338.)
© 1996 American Heart Association, Inc.
Articles |
Levels of Soluble Cell Adhesion Molecules in Patients With Dyslipidemia
From the Sections of Atherosclerosis and Leukocyte Biology, Department of Medicine, Baylor College of Medicine, Houston, Tex.
Correspondence to Christie M. Ballantyne, MD, Department of Internal Medicine, 6565 Fannin St, MS A-601, Houston, TX 77030.
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Abstract |
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 Top Abstract IntroductionMethodsResultsDiscussionReferences |
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Background Increased expression of cell adhesion molecules (CAMs) on the vascular endothelium has been postulated to play an important role in atherogenesis. Both in vitro and in vivo studies have suggested that dyslipidemia may increase expression of CAMs.
Methods and Results To determine whether
dyslipidemia is associated with increased expression of
CAMs, we examined the levels of soluble intercellular adhesion molecule
1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), and
soluble E-selectin (sE-selectin) in individuals with either
hypercholesterolemia or
hypertriglyceridemia and in control
subjects matched for age and sex. Patients with
hypertriglyceridemia had significantly
higher levels of sVCAM-1 (739±69 ng/mL) compared with patients with
hypercholesterolemia (552±63 ng/mL) and
control subjects (480±56 ng/mL). Levels of sICAM-1 were significantly
increased in both the hypercholesterolemic and
hypertriglyceridemic groups (298±29 and
342±31 ng/mL, respectively) compared with the control group (198±14
ng/mL). Levels of sE-selectin were significantly increased in
hypercholesterolemic patients (74±9 ng/mL)
compared with control subjects (48±5 ng/mL). Ten
hypercholesterolemic patients were treated
aggressively with atorvastatin alone or a combination of colestipol and
either atorvastatin or simvastatin for a mean of 42 weeks
and had an average LDL cholesterol reduction of 51%.
Comparison of soluble CAMs before and after treatment showed a
significant reduction only in sE-selectin (77±11 versus 56±6 ng/mL,
P
.03) but not for sVCAM-1 or sICAM-1.
Conclusions Although severe hyperlipidemia is associated with increased levels of soluble CAMs, aggressive lipid-lowering treatment had only limited effects on the levels. Increased levels of soluble CAMs in patients with hyperlipidemia may be a marker for atherosclerosis.
Key Words: lipids • arteriosclerosis • adhesion molecules
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Adhesion and transendothelial migration of circulating leukocytes are critical early events in the pathogenesis of atherosclerosis.1 VCAM-1, ICAM-1, and E-selectin are CAMs that are expressed on endothelial cells and mediate the adhesion of leukocytes to vascular endothelium. In vitro studies have shown that the rolling of monocytes on endothelial cells is mediated at least in part by the interaction of E-selectin and VCAM-1.2 VCAM-1 interacts with the integrins
4ß1 and
4ß7 present on monocytes and lymphocytes, whereas ICAM-1
interacts with the ß2-integrins CD11a, CD11b, and
CD11c.3 The expression of CAMs is stimulated in vitro by
cytokines such as interleukin-1, tumor necrosis factor, and
interferon-
,4 and pathological studies of human
atherosclerosis have shown increased expression of
VCAM-1 and ICAM-1 on endothelial cells, smooth muscle
cells, and macrophages in human atherosclerotic plaques and in
the endothelium of adventitial vessels adjacent to
plaques.5 6 7 E-selectin expression is also increased in
atherosclerosis but is confined to the vascular
endothelium. Animal studies of
hyperlipidemia and diabetes mellitus have demonstrated
increased expression of VCAM-1 and E-selectin associated with
atherosclerosis.8 Lysophosphatidylcholine,
a component of modified LDL, has been shown to upregulate VCAM-1
expression,9 and recent reports suggest that fatty acids
may also modulate expression of VCAM-1.10 11
Unfortunately, determining whether dyslipidemia leads to
increased expression of endothelial CAMs has been
difficult because of the inability to assess the level of adhesion
molecule expression of the vascular endothelium in
vivo. Soluble forms of these adhesion molecules (sVCAM-1, sICAM-1, and sE-selectin) can be detected in the serum and are increased in conditions with an inflammatory component, such as pulmonary fibrosis, vasculitis, melanoma, and heart transplantation.12 13 The mechanism by which levels of soluble CAMs are increased is unknown, but the soluble levels are increased in conditions in which expression on the cell membrane has also been shown to be increased, such as after heart or liver transplantation.13 14 The purpose of this study was twofold. First, we wanted to determine whether patients with severe dyslipidemia due to defects in either LDL or TG metabolism had increased levels of soluble CAMs, and second, we wanted to determine whether aggressive lowering of LDL-C by drug therapy in a subset of patients would lead to a reduction in the levels of soluble CAMs.
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Methods |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Subjects
Three groups of subjects were recruited into a protocol approved by the institutional review board for human subjects. HC subjects (n=14) were identified on the basis of LDL-C level >200 mg/dL and fasting TG level <200 mg/dL on an American Heart Association step I diet without drug therapy for at least 30 days. HTG patients (n=13) were identified on the basis of fasting TG level >475 mg/dL and LDL-C level <180 mg/dL without lipid-lowering therapy. Healthy control subjects (n=13) without major cardiovascular risk factors and with LDL-C level <160 mg/dL and fasting TG level <150 mg/dL were selected to approximate the age and sex distribution of the other groups. Exclusion criteria for all subjects included hypothyroidism, renal disease, malignancy, treatment with immunosuppressive drugs, connective tissue disease, cardiovascular event within 6 months, and any acute illness. In patients with hyperlipidemia, a medical history was taken and a physical examination was performed to determine if they had clinical evidence or symptoms of advanced coronary artery disease, peripheral vascular disease, or cerebrovascular disease. In addition, a risk factor score was derived for each patient by assigning one point for each of the following: diabetes mellitus, hypertension, smoking, clinically manifest atherosclerosis, and hyperlipidemia. Diabetes was defined as a fasting blood glucose level >115 mg/dL or treatment with a hypoglycemic agent. Hypertension was defined as systolic blood pressure >140 mm Hg, diastolic blood pressure >90 mm Hg, or treatment with an antihypertensive agent.
Treatment of Hypercholesterolemic
Subjects
Of the 14 HC subjects, 10 received aggressive treatment for
their hypercholesterolemia for a period of 37
to 46 weeks (mean, 41.6±1.1 weeks). Four patients received
atorvastatin, an experimental 3-hydroxy-3-methylglutaryl coenzyme A
(HMG-CoA) reductase inhibitor, as monotherapy at a dosage
of 80 mg/d. Three patients were treated for 16 weeks with colestipol 20
g/d, then with a combination of colestipol 20 g/d and atorvastatin 40
mg/d for an additional 21 to 30 weeks (mean, 25.7±2.6 weeks). One of
these 3 patients discontinued the colestipol after 17 weeks because of
gastrointestinal complaints and remained on atorvastatin 40 mg/d. The
final 3 patients received colestipol 20 g/d for 16 weeks followed by a
combination of colestipol 20 g/d and simvastatin 40 mg/d
for an additional 21 to 30 weeks (mean, 26±2.6 weeks).
Measurements
Blood samples were obtained by standard venipuncture
after a 12-hour fast from all subjects at baseline. Plasma TC was
measured with either a Hitachi 747 or Cobas-Fara II analyzer
according to CDC reference procedures.15 The same
technique was used to measure HDL-C in control and HC subjects after
precipitation of apo B–containing lipoproteins from samples by the use
of dextran sulfate and magnesium.16 In the HTG subjects,
HDL particles were separated by ultracentrifugation
at a density of 1.125 g/mL, and cholesterol concentration
then was determined by the same methods as described for TC. Plasma TG
was measured after preparation with lipase, glycerol phosphate oxidase,
and peroxidase.17 LDL-C was calculated in the HC patients
and control subjects by the Friedewald equation.18 In the
HTG patients, LDL-C was measured directly after fractionation of the
lipoproteins by differential ultracentrifugation at
density 1.006 g/mL. In the 10 HC subjects who received drug therapy, a
second 20-mL blood sample was collected after treatment, and values for
TC, HDL-C, TG, and LDL-C were obtained by the same techniques described
above. Levels of sICAM-1, sVCAM-1, and sE-selectin were determined by
the use of monoclonal antibody-based ELISA assays (R and D Systems)
on frozen serum collected at baseline from all subjects and after
treatment from the patients who received medication. All samples and
controls were performed in duplicate, and concentrations of samples
were determined by analyzing standards with known concentrations of
recombinant adhesion molecules coincident with samples and plotting a
curve of signal versus concentration.
Statistics
ANOVA with the Bonferroni-Dunn comparison19 was
performed to determine the differences among the three subject groups
in age, baseline lipid levels, and baseline levels of sICAM-1, sVCAM-1,
and sE-selectin. Nonparametric tests (ie, ANOVA on the
ranks rather than on the raw data20 ) were used for TG,
HDL-C, and sICAM-1 because of the large difference in variability among
the groups in these parameters. Simple regression
analysis was used to examine the relation among sICAM-1,
sVCAM-1, and sE-selectin levels. ANOVA on ranked data (Kruskal-Wallis
test) was used to determine if the levels of sICAM-1, sVCAM-1, and
sE-selectin differed among the risk factor categories of the subjects.
For all ANOVAs, pairs of groups were compared only if the overall
comparison was significant (P<.05). Soluble CAM levels in
subjects with atherosclerosis were compared with those
in hyperlipidemic (HC and HTG) subjects without
clinical atherosclerosis using the unpaired Student's
t test. The paired Student's t test was used to
compare lipid levels, sICAM-1, sVCAM-1, and sE-selectin before and
after treatment in the subjects who received drug treatment for
elevated LDL-C. Results are presented as mean±SE.
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Results |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Baseline characteristics of the three groups are shown in the Table
. There were no significant differences in age or
sex among the three groups. The HC group compared with the control
group had a significantly higher TC (345±16 versus 201±9 mg/dL) and
LDL-C (269±16 versus 114±9 mg/dL) and significantly lower HDL-C
(44±2 versus 67±6 mg/dL). The HTG group compared with the control
group had significantly higher TC (311±16 versus 201±9 mg/dL) and TG
(911±111 versus 97±7 mg/dL) and significantly lower HDL-C (20±2
versus 67±6 mg/dL); LDL-C level (116±13 versus 114±9 mg/dL) was not
significantly different from that in the control group.
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The level of sVCAM-1 was significantly increased in the HTG group
(739±69 ng/mL) compared with the HC (552±63 ng/mL) and control
(480±56 ng/mL) groups (Fig 1, top). Levels of sICAM-1
were increased in both the HC and HTG groups (289±29 and 342±31
ng/mL, respectively) compared with the control group (198±14 ng/mL).
Level of sE-selectin was increased in the HC group (74±9 ng/mL)
compared with the control group (48±5 ng/mL). More patients in the HTG
group had other risk factors or clinical evidence of
atherosclerosis; therefore, a second analysis
that considered the presence of these factors was performed to compare
levels of soluble CAMs in the control subjects, subjects with
hyperlipidemia alone (either elevated LDL-C or TG,
n=19), and subjects with hyperlipidemia plus any other
risk factor (n=8). Patients with hyperlipidemia and at
least one other risk factor had significantly higher levels of both
sVCAM-1 and sICAM-1 than the other groups, as shown in the bottom of
Fig 1. The 5 patients with hyperlipidemia and
atherosclerosis had significantly increased
sVCAM-1 compared with the other 22 patients with
hyperlipidemia (977±143 versus 566±37 ng/mL,
P.0004). In the overall study population, there was a
significant correlation between levels of sICAM-1 and sVCAM-1
(r=.56, P.001) and between levels of
sICAM-1 and sE-selectin (r=.61,
P.0001) but not between sVCAM-1 and sE-selectin
(r=.19, P=.25). Because of the small sample size
of this study, we did not perform separate analyses to examine
the role of additional risk factors in patients with
hypercholesterolemia versus
hypertriglyceridemia, nor did we examine
the relative impact of specific risk factors such as diabetes versus
hypertension.
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Lipid-lowering drug treatment effects in the HC patients evaluated
by comparing pretreatment and posttreatment lipid levels showed
reductions of TC (327±15 versus 200±17 mg/dL [39%]) and LDL-C
(252±14 versus 124±17 mg/dL [51%]) without significant changes in
TG (139±19 versus 113±13 mg/dL) or HDL-C (47±3 versus 53±4 mg/dL).
Comparison of soluble CAMs before and after treatment showed a
significant reduction in sE-selectin (77±11 versus 56±6 ng/mL,
P.03) but no significant change in sVCAM-1 (626±76 versus
672±51 ng/mL) or sICAM-1 (314±36 versus 342±36 ng/mL) (Fig 2).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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In this report, we have shown for the first time that severe dyslipidemia is associated with elevated levels of soluble CAMs. Patients with marked elevations of LDL-C had increased levels of sICAM-1 and sE-selectin, whereas patients with severely elevated TG had increased levels of sVCAM-1 and sICAM-1. Patients with severe hypertriglyceridemia also had markedly reduced levels of HDL-C, thus making it unclear which aspect of dyslipidemia was related to the change in soluble CAM levels. One of the questions raised by the association between dyslipidemia and soluble CAM levels is whether dyslipidemia causes endothelial dysfunction that results in increased expression of CAMs and increased release of CAMs into the plasma or whether the increased levels of soluble CAMs are a consequence of atherosclerosis induced by the dyslipidemia. Compared with other subjects, patients with hyperlipidemia and at least one other risk factor, who are more likely to have a greater extent of atherosclerosis, also had increased levels of sVCAM-1 and sICAM-1. In addition, patients who had clinical evidence of atherosclerosis (angina, claudication, or history of carotid endarterectomy) had the highest levels of sVCAM-1 and sICAM-1. Other studies have suggested that atherosclerosis may be associated with increased levels of CAMs. A recent study by Blann and McCollum21 found higher levels of sICAM-1 in patients with peripheral vascular disease (P=.0003) and in patients with ischemic heart disease (P=.0059) than in age-matched control subjects but no significant difference in sVCAM-1. We predicted that if the increased levels of soluble CAMs were secondary to endothelial dysfunction resulting from hyperlipidemia, reduction of LDL-C might lead to reduction in the levels of soluble CAMs. Successful lipid-lowering therapy, which reduced LDL-C a mean of 51%, led to a significant reduction in sE-selectin but no significant reduction in sVCAM-1 or sICAM-1. We hypothesize that this may be because E-selectin differs in mechanisms of gene regulation as reflected by a pattern of expression restricted to endothelial cells, whereas VCAM-1 and ICAM-1 are expressed on endothelial cells and on other cells that are present in atherosclerotic lesions, such as leukocytes and smooth muscle cells. These genes exhibit differences in regulation at the level of transcription in response to oxidation-sensitive pathways as previously reported for in vitro endothelial expression of VCAM-1, ICAM-1, and E-selectin.22 23 We predict that a significant percentage and perhaps the majority of soluble ICAM-1 and VCAM-1 may not arise from arterial endothelial cells. Although one might argue that the length of therapy was insufficient to alter endothelial function, 6 months of less effective LDL-C reduction with lovastatin was sufficient to show improvement in endothelially mediated vasodilatation in response to acetylcholine.24 These data suggest that the increased levels of sICAM-1 and sVCAM-1 in patients with dyslipidemia may be related to underlying atherosclerosis. If the levels of soluble CAMs were related to the extent of vascular disease (atherosclerotic burden) or the activity of atherosclerosis (the rate of progression), then treatment for 6 months would be of insufficient duration to show a significant impact. The Scandinavian Simvastatin Survival Study did not show a significant reduction in clinical events, ie, activity of atherosclerosis, until after 1.5 to 2 years of treatment.25 Angiographic and ultrasound studies show very modest changes in the extent of atherosclerosis even after 2 to 4 years of aggressive lipid-lowering therapy.26 Future studies should examine the effects of longer periods of lipid-lowering therapy on the level of soluble CAMs.
Although treatment of hyperlipidemia in patients with documented atherosclerosis is believed to be cost-effective, considerable controversy exists about the cost-effectiveness of drug treatment for lipids in primary prevention, particularly in women. Noninvasive tests that would help to identify individuals with atherosclerosis who would be at high risk for cardiovascular events would improve the cost-effectiveness of lipid-lowering therapy. Studies are in progress using sera from individual in the Atherosclerosis Risk in Communities study27 to determine whether levels of soluble CAMs can be used as biochemical markers in conjunction with traditional risk factors to identify asymptomatic individuals at high risk for developing cardiovascular events because of atherosclerosis.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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This work was supported in part by NHLBI grant HL-42550 (C.M.B.); American Heart Association, National Sanofi Winthrop Awardee (C.M.B.); Zeneca Pharmaceuticals (C.M.B.); Parke-Davis (W.I.); and Jiohi Medical School (Y.A.). We are grateful to Kerrie Jara for editorial assistance and Rima Maghes for manuscript preparation.
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Footnotes |
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The guest editor for this article was Wayne Alexander, MD, PhD, Emory University Medical School, Atlanta, Ga.
Received August 14, 1995; revision received February 5, 1996; accepted February 5, 1996.
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G. Desideri, M. C. Marinucci, G. Tomassoni, P. G. Masci, A. Santucci, and C. Ferri Vitamin E Supplementation Reduces Plasma Vascular Cell Adhesion Molecule-1 and von Willebrand Factor Levels and Increases Nitric Oxide Concentrations in Hypercholesterolemic Patients J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2940 - 2945. [Abstract] [Full Text] [PDF]
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L. Calabresi, M. Gomaraschi, B. Villa, L. Omoboni, C. Dmitrieff, and G. Franceschini Elevated Soluble Cellular Adhesion Molecules in Subjects With Low HDL-Cholesterol Arterioscler Thromb Vasc Biol, April 1, 2002; 22(4): 656 - 661. [Abstract] [Full Text] [PDF]
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 A. Silvestro, G. Oliva, and G. Brevetti Intermittent claudication and endothelial dysfunction Eur. Heart J. Suppl., March 1, 2002; 4(suppl_B): B35 - B40. [Abstract] [PDF]
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C. Pallaud, R. Gueguen, C. Sass, M. Grow, S. Cheng, G. Siest, and S. Visvikis Genetic influences on lipid metabolism trait variability within the Stanislas Cohort J. Lipid Res., November 1, 2001; 42(11): 1879 - 1890. [Abstract] [Full Text] [PDF]
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P. Poredos State-of-the-Art Review: Endothelial Dysfunction in the Pathogenesis of Atherosclerosis Clinical and Applied Thrombosis/Hemostasis, October 1, 2001; 7(4): 276 - 280. [Abstract] [PDF]
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A. E. Hak, H. A. P. Pols, C. D. A. Stehouwer, J. Meijer, A. J. Kiliaan, A. Hofman, M. M. B. Breteler, and J. C. M. Witteman Markers of Inflammation and Cellular Adhesion Molecules in Relation to Insulin Resistance in Nondiabetic Elderly: The Rotterdam Study J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4398 - 4405. [Abstract] [Full Text] [PDF]
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A. Yildirir, S. L. Tokgozoglu, I. Haznedaroglu, I. Sinici, G. Kabakci, K. Ovunc, S. Aksoyek, A. Oto, F. Ozmen, S. Kirazli, et al. Extent of Coronary Atherosclerosis and Homocysteine Affect Endothelial Markers Angiology, September 1, 2001; 52(9): 589 - 596. [Abstract] [PDF]
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P. Libby Current Concepts of the Pathogenesis of the Acute Coronary Syndromes Circulation, July 17, 2001; 104(3): 365 - 372. [Full Text] [PDF]
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 E Sbarouni, C Kroupis, Z.S Kyriakides, K Koniavitou, and D.T Kremastinos Cell adhesion molecules in relation to simvastatin and hormone replacement therapy in coronary artery disease Eur. Heart J., June 2, 2000; 21(12): 975 - 980. [Abstract] [PDF]
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K. J. Williams, R. Scalia, K. D. Mazany, W. V. Rodrigueza, and A. M. Lefer Rapid Restoration of Normal Endothelial Functions in Genetically Hyperlipidemic Mice by a Synthetic Mediator of Reverse Lipid Transport Arterioscler Thromb Vasc Biol, April 1, 2000; 20(4): 1033 - 1039. [Abstract] [Full Text] [PDF]
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J. R. Chan, R. H. Boger, S. M. Bode-Boger, O. Tangphao, P. S. Tsao, T. F. Blaschke, and J. P. Cooke Asymmetric Dimethylarginine Increases Mononuclear Cell Adhesiveness in Hypercholesterolemic Humans Arterioscler Thromb Vasc Biol, April 1, 2000; 20(4): 1040 - 1046. [Abstract] [Full Text] [PDF]
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C.-L. Chao, T.-L. Kuo, and Y.-T. Lee Effects of Methionine-Induced Hyperhomocysteinemia on Endothelium-Dependent Vasodilation and Oxidative Status in Healthy Adults Circulation, February 8, 2000; 101(5): 485 - 490. [Abstract] [Full Text] [PDF]
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A. H. Wagner, T. Kohler, U. Ruckschloss, I. Just, and M. Hecker Improvement of Nitric Oxide-Dependent Vasodilatation by HMG-CoA Reductase Inhibitors Through Attenuation of Endothelial Superoxide Anion Formation Arterioscler Thromb Vasc Biol, January 1, 2000; 20(1): 61 - 69. [Abstract] [Full Text] [PDF]
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 C. Ferri, G. Desideri, M. Valenti, C. Bellini, M. Pasin, A. Santucci, and Giancarlo De Mattia Early Upregulation of Endothelial Adhesion Molecules in Obese Hypertensive Men Hypertension, October 1, 1999; 34(4): 568 - 573. [Abstract] [Full Text] [PDF]
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L. E. P. Rohde, C. H. Hennekens, and P. M. Ridker Cross-Sectional Study of Soluble Intercellular Adhesion Molecule-1 and Cardiovascular Risk Factors in Apparently Healthy Men Arterioscler Thromb Vasc Biol, July 1, 1999; 19(7): 1595 - 1599. [Abstract] [Full Text] [PDF]
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 M. Pahor, M. B. Elam, R. J. Garrison, S. B. Kritchevsky, and W. B. Applegate Emerging Noninvasive Biochemical Measures to Predict Cardiovascular Risk Arch Intern Med, February 8, 1999; 159(3): 237 - 245. [Abstract] [Full Text] [PDF]
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K. K. Koh, C. Cardillo, M. N. Bui, L. Hathaway, G. Csako, M. A. Waclawiw, J. A. Panza, and R. O. Cannon III Vascular Effects of Estrogen and Cholesterol-Lowering Therapies in Hypercholesterolemic Postmenopausal Women Circulation, January 26, 1999; 99(3): 354 - 360. [Abstract] [Full Text] [PDF]
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 S. Allen, S. Khan, S.-p. Tam, M. Koschinsky, P. Taylor, and M. Yacoub Expression of adhesion molecules by Lp(a): a potential novel mechanism for its atherogenicity FASEB J, December 1, 1998; 12(15): 1765 - 1776. [Abstract] [Full Text]
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K. N. Islam, S. Devaraj, and I. Jialal {alpha}-Tocopherol Enrichment of Monocytes Decreases Agonist-Induced Adhesion to Human Endothelial Cells Circulation, November 24, 1998; 98(21): 2255 - 2261. [Abstract] [Full Text] [PDF]
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Y. Abe, B. El-Masri, K. T. Kimball, H. Pownall, C. F. Reilly, K. Osmundsen, C. W. Smith, and C. M. Ballantyne Soluble Cell Adhesion Molecules in Hypertriglyceridemia and Potential Significance on Monocyte Adhesion Arterioscler Thromb Vasc Biol, May 1, 1998; 18(5): 723 - 731. [Abstract] [Full Text] [PDF]
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G. Davi, M. Romano, A. Mezzetti, A. Procopio, S. Iacobelli, T. Antidormi, T. Bucciarelli, P. Alessandrini, F. Cuccurullo, and G. B. Bon Increased Levels of Soluble P-Selectin in Hypercholesterolemic Patients Circulation, March 17, 1998; 97(10): 953 - 957. [Abstract] [Full Text] [PDF]
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S.-J. Hwang, C. M. Ballantyne, A. R. Sharrett, L. C. Smith, C. E. Davis, A. M. Gotto Jr, and E. Boerwinkle Circulating Adhesion Molecules VCAM-1, ICAM-1, and E-selectin in Carotid Atherosclerosis and Incident Coronary Heart Disease Cases : The Atherosclerosis Risk In Communities (ARIC) Study Circulation, December 16, 1997; 96(12): 4219 - 4225. [Abstract] [Full Text]
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R. De Caterina, G. Basta, G. Lazzerini, G. Dell'Omo, R. Petrucci, M. Morale, F. Carmassi, and R. Pedrinelli Soluble Vascular Cell Adhesion Molecule-1 as a Biohumoral Correlate of Atherosclerosis Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 2646 - 2654. [Abstract] [Full Text]
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T. Sampietro, M. Tuoni, M. Ferdeghini, A. Ciardi, P. Marraccini, C. Prontera, G. Sassi, M. Taddei, and A. Bionda Plasma Cholesterol Regulates Soluble Cell Adhesion Molecule Expression in Familial Hypercholesterolemia Circulation, September 2, 1997; 96(5): 1381 - 1385. [Abstract] [Full Text]
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C. Wayne Smith Potential Significance of Circulating E-Selectin Circulation, April 15, 1997; 95(8): 1986 - 1988. [Full Text]
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K. Peter, P. Nawroth, C. Conradt, T. Nordt, T. Weiss, M. Boehme, A. Wunsch, J. Allenberg, W. Kubler, and C. Bode Circulating Vascular Cell Adhesion Molecule-1 Correlates With the Extent of Human Atherosclerosis in Contrast to Circulating Intercellular Adhesion Molecule-1, E-Selectin, P-Selectin, and Thrombomodulin Arterioscler Thromb Vasc Biol, March 1, 1997; 17(3): 505 - 512. [Abstract] [Full Text]
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L. Calabresi, M. Gomaraschi, B. Villa, L. Omoboni, C. Dmitrieff, and G. Franceschini Elevated Soluble Cellular Adhesion Molecules in Subjects With Low HDL-Cholesterol Arterioscler Thromb Vasc Biol, April 1, 2002; 22(4): 656 - 661. [Abstract] [Full Text] [PDF]
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