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CLINICAL RESEARCH: CORONARY ARTERY DISEASE

Association of Plasma Levels of F11 Receptor/Junctional Adhesion Molecule-A (F11R/JAM-A) With Human Atherosclerosis

Erdal Cavusoglu, MD^_*,,_*, Elizabeth Kornecki, PhD, Malgorzata B. Sobocka, PhD, Anna Babinska, PhD, Yigal H. Ehrlich, PhD^||, Vineet Chopra, MD, Sunitha Yanamadala, PhD^#, Cyril Ruwende, MD, PhD^#, Moro O. Salifu, MD, Luther T. Clark, MD, FACC^_*, Calvin Eng, MD, FACC, David J. Pinsky, MD, FACC^# and Jonathan D. Marmur, MD, FACC^_*

^_* Division of Cardiology, Department of Medicine, State University of New York Downstate Medical Center, Brooklyn, New York
Division of Nephrology, Department of Medicine, State University of New York Downstate Medical Center, Brooklyn, New York
Department of Anatomy and Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York
Department of Medicine, Bronx Veterans Affairs Medical Center, Bronx, New York
^|| Program in Neuroscience, College of Staten Island of the City University of New York, Staten Island, New York
^# Division of Cardiovascular Medicine, Department of Medicine, University of Michigan, Ann Arbor, Michigan

Manuscript received March 13, 2007; revised manuscript received May 3, 2007, accepted May 28, 2007.

^_* Reprint requests and correspondence: Dr. Erdal Cavusoglu, SUNY Health Science Center at Brooklyn, 450 Clarkson Avenue, Box 1257, Brooklyn, New York 11203-2098. (Email: ecavusoglu{at}aol.com).

Objectives: The purpose of this study was to determine the association of the F11 receptor (F11R) with human vascular disease.

Background: A molecule identified as critical for platelet adhesion to a cytokine-inflamed endothelial surface in vitro is F11R. The F11R is known to be expressed in platelets and endothelium and reported recently to be overexpressed in atherosclerotic plaques.

Methods: A novel enzyme-linked immunosorbent assay was developed for the measurement of soluble F11R in human plasma. The F11R levels, along with a number of other biomarkers, were measured in 389 male patients with known or suspected coronary artery disease (CAD) undergoing coronary angiography at a Veterans Administration Medical Center.

Results: Patients with normal or nonobstructive disease (CAD angiographic score of 0), mild-to-moderate disease (score of 1 to 3), and severe disease (score of 4 to 6) had median F11R plasma levels of 38.6 pg/ml (mean 260 ± 509.6 pg/ml), 45.2 pg/ml (mean 395.3 ± 752.7 pg/ml), and 105.8 pg/ml (mean 629 ± 831.7 pg/ml), respectively (p = 0.03). By multivariate analysis, the variables independently associated with CAD score were age, hyperlipidemia, chronic renal insufficiency, left ventricular function, and plasma F11R levels. The F11R was the only biomarker that was independently associated with CAD score. Consistent with the previously reported effects of tumor necrosis factor (TNF)-alpha on F11R expression in cultured endothelial cells, F11R levels correlated strongly with plasma TNF-alpha levels (r = 0.84; p < 0.0001).

Conclusions: Plasma F11R is independently associated with the presence and severity of angiographically defined CAD. By virtue of its strong correlation to plasma TNF-alpha, F11R may be an important mediator of the effects of inflammation on the vessel wall. Strategies that block F11R may represent a novel approach to the treatment of human atherosclerosis.

Abbreviations and Acronyms   BSA = bovine serum albumin   CAD = coronary artery disease   CRI = chronic renal insufficiency   ELISA = enzyme-linked immunosorbent assay   ESR = erythrocyte sedimentation rate   F11R = F11 receptor   HRP = horseradish peroxidase   hs-CRP = high-sensitivity C-reactive protein   JAM-A = junctional adhesion molecule-A   LV = left ventricular   MI = myocardial infarction   MMP = matrix metalloproteinase   PAI = plasminogen activator inhibitor   PBS = phosphate-buffered saline   RANTES = regulated upon activation, normal T-cell expressed and secreted   TIMP = tissue inhibitor of metalloproteinase   TNF = tumor necrosis factor

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