The role of interleukin 18 in the pathogenesis of hypertension-induced vascular disease.
Understanding the mechanism by which chronic high blood pressure induces vascular disease is of fundamental importance for prevention of the adverse consequences of hypertension. Clinical and population studies have consistently found increased circulating levels of interleukin 18 (IL-18) in patients with hypertension. Although obesity, and possibly age, is a determinant of plasma IL-18 levels, the relationship of IL-18 to hypertension seems to be independent of these factors. Experimental evidence indicates that the expression of IL-18 and/or its receptor can be induced by catecholamines or angiotensin, two factors that are involved in the pathophysiology of hypertension. Elevated circulating IL-18 levels are associated with vascular changes in the carotid artery, including increased carotid intima-media thickness, which, in turn, is a predictor of cardiovascular events in patients with established coronary disease. IL-18, either directly or through oxidative stress pathways and matrix metalloproteins, can alter endothelial function or induce vascular smooth muscle cell migration and/or proliferation to produce the vascular changes that occur with hypertension. This Review examines the data on IL-18 and hypertensive vascular disease, and explores the potential cellular and molecular mechanisms that might connect hypertension to vascular disease.
Rabkin
Simon W
SW
Department of Medicine, University of British Columbia, Vancouver, BC, Canada. rabkin@interchange.ubc.ca
D000809:Angiotensins / Q000097:blood; D002395:Catecholamines / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000150:complications* / Q000503:physiopathology; D020382:Interleukin-18 / Q000097:blood*; D020782:Matrix Metalloproteinases / Q000097:blood; D018384:Oxidative Stress; D016491:Peripheral Vascular Diseases / Q000097:blood* / Q000209:etiology* / Q000503:physiopathology
D000809:Angiotensins; D002395:Catecholamines; D020382:Interleukin-18; D020782:Matrix Metalloproteinases