Abstract 509: Early Pathogenesis of Murine Aortic Valve Disease is Marked by Versican-Rich Proteoglycan Synthesis

Background: Aortic valve disease (AVD) is a cell-mediated pathology without pharmacotherapy whose early pathogenesis is poorly understood. In mice, the study of later-stage fibrotic & calcific AVD requires aggressive dietary/genetic induction unsuitable for the study of early AVD progression. Here, we examined the initial extracellular matrix & cellular changes induced in the mouse aortic valve by a mildly atherogenic diet. Methods: Male WT C57Bl/6J mice were fed control or high-fat (HF, BioServ F3282) diets for 4 or 16 months (n = 6-10 per group). Aortic valve function was assessed by echocardiography. Valve sections were (immuno)stained for Movat’s pentachrome, proteoglycans (PG), Sox9, & αSMA. Valve interstitial cells (VICs) from porcine aortic valves were cultured with 5 ng/ml TGF-β1 for 5 days. PG synthesis & mRNA levels were measured by g-HCL & qPCR, respectively. Results: At 4 months, valve function was unaffected by the HF diet (transvalvular velocity: 123.5 ± 8.5 vs. 128.2 ± 9.2 cm/s, p = 0.75), ...