Is angiotensin II receptor activation involved in the mechanism and pathophysiological role of oxidized LDL?

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In this study, we investigated our hypothesis that the angiotensin II type 1 receptor (AT1) is involved in the oxidized LDL (oxLDL)-induced vascular responses involved in the pathogenesis of cardiovascular disease. We found that both the lectin like oxLDL receptor (LOX-1) and AT1 are required for the ability of oxLDL to activate cell signaling and that LOX-1 and AT1 form receptor complexes on cell surface membranes. Mutations in AT1 greatly reduced the capacity of oxLDL to activate G protein and MAP kinase. In addition, oxLDL induced acute blood pressure elevations in mice and these hypertensive effects were totally abolished by deletion of AT1a or LOX-1. In addition, oxLDL-induced impairment of endothelial-dependent vascular relaxation was abolished by ARB or genetic deletion of AT1 in mice. These findings indicate that oxLDL-induced activation of AT1 constitutes a heretofore unrecognized mechanism that could further contribute to the effects of oxLDL on risk for atherosclerosis.