title: Mechanisms linking angiotensin II and atherogenesis.
abstract: OBJECTIVE
  The concept that angiotensin II plays a central role in early atherogenesis, progression to atherosclerotic plaque, and the most serious clinical sequelae of coronary artery disease is the subject of considerable current interest. Results from recent large clinical trials confirm that blunting of the renin-angiotensin system through either angiotensin converting enzyme inhibition or angiotensin II type 1 receptor blockade incurs significant beneficial outcomes in patients with coronary artery disease. The exact mechanisms for these effects are not yet clear, but are suggested by studies demonstrating that suppression of the renin-angiotensin system is associated with muted vascular oxidative stress.
  
  
  RESULTS
  As most of the biological effects of the renin-angiotensin system occur through stimulation of the angiotensin II type 1 receptor, the focus of this review is on changes in the vascular wall mediated by this receptor and primarily related to endothelial and vascular smooth muscle cells, monocyte/macrophages and platelets. The interactions between angiotensin II and nitric oxide exert particular demands on the vascular capacity to adapt to dyslipidemia, hypertension, estrogen deficiency and diabetes mellitus that appear to exacerbate atherogenesis. Associated with each of these conditions is angiotensin II-mediated stimulation of macrophages, platelet aggregation, plasminogen activator inhibitor 1, endothelial dysfunction, vascular smooth muscle cell proliferation and migration, apoptosis, leukocyte recruitment, fibrogenesis and thrombosis.
  
  
  CONCLUSIONS
  Inhibition of the actions of angiotensin II serves a dual purpose: indirectly through reduction of mechanical stress on the vascular wall, and directly by diminished stimulation for vascular restructuring and remodeling. Collectively, data from studies published over the last year confirm and extend the notion that angiotensin II is a true cytokine prevalent at all stages of atherogenesis.
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D018384:Oxidative Stress
chemical_list: D000804:Angiotensin II