Role of angiotensin II type 1 receptor in the regulation of cellular adhesion molecules in atherosclerosis

A. Prasad, K. K. Koh, W. H. Schenke, R. Mincemoyer, G. Csako, T. A. Fleischer, M. Brown, T. A. Selvaggi, A. A. Quyyumi

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65 Scopus citations

Abstract

Background: Inflammation is a central feature of coronary artery disease (CAD) that is characterized by increased expression of cellular adhesion molecules with the exception of L-selectin. L-selectin is a leukocyte adhesion molecule that is rapidly shed after leukocyte activation so that it appears to be decreased in CAD. The renin-angiotensin system (RAS) is implicated in atherogenesis and up-regulates these molecules. Objectives: The aim of this study was to investigate the effect of angiotensin type 1 (AT1) receptor antagonism on serum and leukocyte adhesion molecule expression in patients with CAD. Blood samples were collected from 31 patients before and after 8 weeks of treatment with losartan (44 ± 2 mg/d, mean ± SE), an AT1 receptor antagonist. We measured serum intercellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial-leukocyte adhesion molecule, and C-reactive protein (CRP). By flow cytometry, we also measured the expression of leukocyte CD11a, CD11b, CD11c, CD18, CD31, CD49d, and CD62L (L-selectin) in 13 patients. Results: Treatment with losartan decreased systolic blood pressure (141 ± 3 vs 135 ± 4 mm Hg, P = .04) and increased plasma renin activity (1.2 ± 0.4 vs 2.7 ± 0.5 ng/mL/h, P = .001). There was a significant increase in L-selectin expression on monocytes (86 ± 6 vs 118 ± 10 MESF units, P = .007), lymphocytes (52 ± 10 vs 79 ± 8, P = .01), and granulocytes (124 ± 7 vs 156 ± 18, P = .056). However, there were no changes in the other leukocyte and serum adhesion molecules or CRP. Conclusions: These findings suggest that AT1 receptor antagonism selectively modulates L-selectin expression on leukocytes and that endogenous stimulation of AT1 receptors by the RAS contributes to the activation of leukocytes and decreased expression of L-selectin in CAD.

Original languageEnglish (US)
Pages (from-to)248-253
Number of pages6
JournalAmerican Heart Journal
Volume142
Issue number2
DOIs
StatePublished - 2001
Externally publishedYes

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ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Prasad, A., Koh, K. K., Schenke, W. H., Mincemoyer, R., Csako, G., Fleischer, T. A., Brown, M., Selvaggi, T. A., & Quyyumi, A. A. (2001). Role of angiotensin II type 1 receptor in the regulation of cellular adhesion molecules in atherosclerosis. American Heart Journal, 142(2), 248-253. https://doi.org/10.1067/mhj.2001.116699