Role of the renin-angiotensin-aldosterone system and proinflammatory mediators in cardiovascular disease.
Inflammation is a key mechanism in the initiation, progression, and clinical sequelae of cardiovascular diseases (CVDs), including atherosclerosis, nephropathy, and cardiomyopathy. Angiotensin II, the major effector peptide of the renin-angiotensin-aldosterone system (RAAS), plays a significant role in the advent and perpetuation of these inflammatory diseases, most notably in atherogenesis. Consequently, suppression of the influence of angiotensin II by angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers may reduce or potentially reverse atherosclerosis and other inflammation-associated CVDs. Angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors exert anti-inflammatory actions and prevent or reduce the development of atherosclerosis in animal models. Clinically, RAAS suppression reduces common carotid and femoral artery intima-media thickness, thus indicating moderation of the vascular disease process. These clinical benefits likely involve restraint of the deleterious effects of angiotensin II in addition to, or independent of, lowering blood pressure. Increasing evidence that the detection and monitoring of vascular inflammation are important tools in the management of atherosclerosis also implicates the RAAS in this pathogenic process. Inflammatory molecules such as intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, and C-reactive protein have potential diagnostic and prognostic values in CVD and are modified by angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. Monitoring these markers may be crucial for determining which agents, or combinations of agents, will result in the most clinically beneficial outcomes for patients. Large-scale trials are still required to determine the effects of the long-term suppression of inflammation on CVDs through the use of RAAS modulating agents, as well as to determine how closely markers of inflammatory activity may correlate with CVD outcomes.
Ferrario
Carlos M
CM
Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. cferrari@wfubmc.edu
Strawn
William B
WB
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000502:physiology; D002097:C-Reactive Protein; D002318:Cardiovascular Diseases / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology*; D019040:E-Selectin / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000188:drug therapy; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D007378:Interleukins / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha
D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D019040:E-Selectin; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein