Renin-angiotensin system as a therapeutic target in managing atherosclerosis.
Clinical and experimental evidence suggests that the pathways by which hypertension and dyslipidemia lead to vascular disease may overlap and that angiotensin II (Ang II) is involved in restructuring of the arterial wall in both atherosclerosis and hypertension. Ang II represents a potent proinflammatory agent promoting recruitment of monocytes into the vascular intima. Ang II also indirectly facilitates transformation of macrophages and smooth muscle cells into foam cells by promoting superoxide radical formation (via NADP/NADPH oxidase stimulation). The oxidative stress produced by Ang II leads to enhanced low-density lipoprotein oxidation and degradation of nitric oxide, an important vascular protective molecule capable of retarding atherosclerosis progression. The importance of the renin-angiotensin system (RAS) in atherogenesis is highlighted by studies in animal models as well as human beings indicating that inhibition of angiotensin-converting enzyme or blockade of type 1 Ang II receptors retards the development of atherosclerotic lesions. In light of a causal and central role of Ang II in atherogenesis, blockade of the RAS represents an important therapeutic consideration in the prevention and treatment of atherosclerotic disease.
Ferrario
Carlos M
CM
The Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Medical School Boulevard, Winston-Salem, NC 27157, USA. cferrari@wfubmc.edu
Richmond
Renee S
RS
Smith
Ronald
R
Levy
Pavel
P
Strawn
William B
WB
Kivlighn
Salah
S
D000804:Angiotensin II / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D006973:Hypertension / Q000150:complications; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000804:Angiotensin II