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.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine