ABSTRACT
Hypertension and hypercholesterolemia, two major risk factors for atherosclerotic disease, frequently coexist in patients with hypertension and CAD. Data from clinical studies suggest the existence of lipoprotein-neurohormonal interactions that may adversely affect vascular structure and reactivity. Data from preclinical studies suggest that RAS may be upregulated by abnormal lipids, most likely via production of ox-LDL. On the other hand, activation of RAS leads to release of ROS and transcriptional upregulation of LDL and ox-LDL uptake in macrophages, smooth muscle cells and endothelial cells. These findings extend our understanding of the interplay among risk factors to synergistically increase cardiovascular risk, and of the anti-atherosclerotic effects of local ACE inhibition to reduce cardiovascular risk. Trials aimed at modifying RAS along with drugs lowering total- and LDL-cholesterol levels and inhibitors of oxidative modification of LDL-cholesterol will address the clinical relevance of this biological interaction.