Abstract 646: Locked Nucleic Acid miR-143 Ameliorates Aortic Valve Functions in a ROS-Mediated Murine Model of Aortic Valve Sclerosis

Background: Calcific Aortic Valve Disease (CAVD) is the leading cause of valve replacement in the US. While the final stages (Aortic Stenosis -AS) are well described, subclinical stages (Aortic Sclerosis -AVSc) remain understudied. We reported accumulation of Reactive Oxygen Species (ROS) in subclinical stages. Adeno-delivery of antioxidant enzymes rescues Valve Interstitial Cells (VICs) from calcification and osteogenic activation. Furthermore we described OPN-CD44 axis as a calcium-derepression system in AVSc and developed a ROS-mediated murine model based on Angiotensin II infusion that mimic AV remodeling as in AVSc. Here we aim to identify oxidative products able to mediate the transition from AVSc to AS and to test them in vivo. Methods: Oxidized amino-acids were quantified by mass spectrometry (LC MS/MS) on human AVs. Osteogenic-induced VICs and explanted tissues were tested for miR143 expression. C57BL/6J mice were fed an enriched diet and infused with saline (n=24) or AngII (1,000 ng/kg/min) (n=4...