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

Background Inflammation is a central feature of coronary artery disease (CA D) that is characterized by increased expression of cellular adhesion molec ules with the exception of L-selectin. L-selectin is a leukocyte adhesion m olecule 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 angiotens in type I (ATI) receptor antagonism on serum and leukocyte adhesion molecul e expression in patients with CAD. Blood samples were collected from 31 pat ients before and after 8 weeks of treatment with losartan (44 +/-2 mg/d, me an SE), an ATI receptor antagonist. We measured serum intercellular adhesio n molecule-1, vascular cell adhesion molecule-1, endothelial-leukocyte adhe sion molecule, and C-reactive protein (CRP). By flow cytometry, we also mea sured the expression of leukocyte CD11a, CD11b, CD11c, CD18, CD31, CD49d, a nd 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-sele ctin expression an monocytes (86 +/-6 vs 118 +/- 10 MESF units, P=.007), ly mphocytes (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 stimulat ion of AT1 receptors by the RAS contributes to the activation of leukocytes and decreased expression of L-selectin in CAD.