Abstract 1736: Vitamin D Activation Inhibits Atherosclerosis in a Pro-inflammatory Model of Activated Renin-Angiotensin System
Vitamin D activation is anti-inflammatory and vitamin D analogs have been shown to exert inhibitory effects on renin-angiotensin system (RAS). Activation of RAS by angiotensin II strongly induces inflammation and accelerates atherosclerotic lesion development. However, the ability of vitamin D analogs to inhibit vascular inflammation and atherosclerosis remains largely unknown. In this study we determined the effect of vitamin D analog, paricalcitol (PC, Zemplar) on AngII-accelerated atherosclerosis in low-density lipoprotein receptor-deficient (LDLR−/−) mice, fed Western diet and infused with Ang-II. Mice were administered either the vehicle or a non-calcemic dose of PC by subcutaneous injection three times weekly. Four weeks after the injection, quantification of atherosclerosis by en face method revealed that a low-dose PC (0.033 microgram/kg/body weight) significantly inhibited atherosclerosis (79% reduction, p < 0.01 vs. vehicle). PC treatment had no effect on body weights, plasma cholesterol, triglyceride, and glucose or calcium levels. The effect of PC on systemic inflammation was determined by measuring plasma pro-inflammatory/atherogenic markers. PC treatment significantly reduced plasma MCP-1, PAI-1 and leptin levels. Although PC reduced plasma insulin levels, there were no changes in either adiponectin or resistin levels. These data demonstrate that vitamin D activation by a low-dose PC exerts anti-inflammatory and atheroprotective effects and a potential therapeutic strategy to target rapid atherosclerotic lesion development mediated by AngII activation of renin-angiotensin system associated with the metabolic syndrome.