Vascular Cav1.2 Expression is Increased in Atherosclerosis

Abstract

Vascular Ca2+ channels play an important role in the pathogenesis of hypertension, but little is known about their role in atherosclerosis. We studied the expression and function of CaV1.2 in aorta from LDLR -/- mice fed normal or high cholesterol (HC) diet for 26 weeks. HC diet markedly increased serum triglyceride, total cholesterol and phopholipid levels and generated atherosclerotic plaques, but had no significant effect on blood pressure. Immunohistochemistry (Figure) and Western blot analysis (inset) revealed that aortic CaV1.2 expression was significantly upregulated in mice fed HC diet compared to normal (N) diet. The majority of the CaV1.2 expression was in vascular smooth muscle cells (VSMCs), rather than atherosclerotic plaques. Despite overexpression of CaV1.2 subunits, aortic rings from the HC mice had a diminished constrictor response to CaV1.2 channel activator FPL64176, perhaps a result of reduced expression of the contractile protein α-actin. Inclusion of 1 mg/kg/d rosuvastatin or amlodipine in the HC diet ameliorated all observed changes. These data suggest that during atherosclerosis: (1) VSMCs develop a phenotype switch involving upregulation of CaV1.2 subunits but downregulation of contractile protein α-actin, and therefore reduced contractility; (2) CaV1.2 channels may be involved in atherosclerosis.View Large Image | View Hi-Res Image | Download PowerPoint Slide