title: Role of angiotensin II type 1 receptor in the regulation of cellular adhesion molecules in atherosclerosis.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1650, USA.
authors.forename: A
authors.initials: A
authors.lastname: Prasad
authors.forename: K K
authors.initials: KK
authors.lastname: Koh
authors.forename: W H
authors.initials: WH
authors.lastname: Schenke
authors.forename: R
authors.initials: R
authors.lastname: Mincemoyer
authors.forename: G
authors.initials: G
authors.lastname: Csako
authors.forename: T A
authors.initials: TA
authors.lastname: Fleischer
authors.forename: M
authors.initials: M
authors.lastname: Brown
authors.forename: T A
authors.initials: TA
authors.lastname: Selvaggi
authors.forename: A A
authors.initials: AA
authors.lastname: Quyyumi
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000187:drug effects / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000187:drug effects* / Q000276:immunology; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D019040:E-Selectin / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000276:immunology; D019041:L-Selectin / Q000276:immunology; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects / Q000276:immunology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D002097:C-Reactive Protein; D019808:Losartan