Abstract 348: Dietary Quercetin Prevents Warfarin-Induced Vascular Calcification in Rats

Medial arterial calcification contributes to the development of isolated systolic hypertension, the most frequent type of blood pressure elevation in the elderly; complicates a variety of prevalent disorders such as diabetes and renal disease; and can develop in response to warfarin - the staple in anticoagulant therapy to millions of people. Our in vitro studies have shown that the bioflavonoid quercetin effectively prevents warfarin-induced vascular calcification in VSMCs and identified b-catenin signaling as a specific target of this effect. Here, we have tested in vivo the association of b-catenin signaling with warfarin-induced calcification and the efficacy of quercetin in preventing warfarin-induced aortic calcium accrual. Vitamin K-warfarin treatment was used for 4 weeks to induce arterial calcification in male rats. Molecular analysis demonstrates activation of b-catenin signaling in the calcified areas and osteoblast-like transformation in vascular cells. Dietary quercetin (10 mg/kg body weight) (Quercegen Pharma, Newton, MA) efficiently prevents warfarin-induced calcification (3.04+/-0.45 ug Ca in vitamin K-warfarin animals vs 0.77+/-0.08 ug Ca in quercetin supplementation per mg dry arterial tissue (n=5; p<0.05). In parallel, quercetin inhibits b-catenin signaling and phenotypic transformation in vascular smooth muscle analyzed by expression of transcription factor Runx2, collagen type I and osteocalcin. Further, quercetin diet enhances expression of VSMC markers smooth muscle actin, myosin heavy chain, sm22a and calponin, suggesting a stabilized smooth muscle phenotype of these cells. No toxic or systemic effects of quercetin treatment were observed, identifying this bioflavonoid as a putative therapeutic for vascular calcification.