Theodore Cooper Memorial Lecture. Hypertension and the pathogenesis of atherosclerosis. Oxidative stress and the mediation of arterial inflammatory response: a new perspective.
Hypertension is a risk factor for the development of atherosclerosis, although the mechanisms have not been well elucidated. As the cellular and molecular mechanisms of the pathogenesis of atherosclerosis and the effects of hypertension are being more clearly defined, it becomes apparent that the two processes have certain common mechanisms. The endothelium is a likely central focus for the effect of both diseases. There is increasing evidence that atherosclerosis should be viewed fundamentally as an inflammatory disease. Atherogenic stimuli such as hyperlipidemia appear to active the inflammatory response by causing expression of mononuclear leukocyte recruiting mechanisms. The gene for one of these, the vascular cell adhesion molecule-1, is controlled at least in part by transcriptional factors regulated by oxidative stress, which modifies the redox state of the endothelial cell. Alterations in the redox state of the arterial wall also may contribute to vascular smooth muscle cell growth. In a somewhat parallel fashion, there is evidence that hypertension may also exert oxidative stress on the arterial wall. This article reviews evidence that leads to the postulate that hypertension predisposes to and accelerates atherosclerosis at least in part because of synergy between elevated blood pressure and other atherogenic stimuli to induce oxidative stress on the arterial wall.
Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322.
R W
RW
Alexander
D000818:Animals; D001158:Arteries / Q000378:metabolism; D001161:Arteriosclerosis / Q000209:etiology* / Q000378:metabolism; D001167:Arteritis / Q000209:etiology; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications; D006973:Hypertension / Q000150:complications* / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress