522 The molecular mechanisms of the initial step of atherosclerosis : The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) mediated the lipid accumulation
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Hypertension is a powerful independent risk factor for atherosclerotic cardiovascular diseases; however, the precise molecular mechanisms whereby hypertension promotes atherosclerotic formation remain to be determined. The interaction of oxidized low density lipoprotein (LDL) and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) plays a critical role in atherogenesis. To investigate their specific roles in acceleration of atherogenesis by hypertension, here, we employed stroke prone spontaneously hypertensive rats (SHR-SP), models of human essential hypertension, rapidly developed arterial lipid deposition in mesenteric arteries when fed on high fat diet and salt loading. These vascular lipid deposition lesions share similar characteristics of the initial lesions of atherosclerosis. The enhanced LOX-1 expression in SHR-SP was closely associated with deposited lipids, oxidized LDL, and generation of reactive oxygen species. Anti-LOX-1 neutralizing antibody dramatically suppressed lipid deposition in vivo in SHR-SP. Vitamin E decreased plasma oxidized LDL, which suppressed the lipid deposition as well. Furthermore, anti-LOX-1 antibody suppressed the increase in vascular permeability and uptake of oxidized LDL in SHR-SP. Thus, the enhanced expression and activation of LOX-1 leading to an increase in vascular permeability and oxidative stress plays an essential role in vascular lipid deposition under hypertensive states.
