Abstract 20563: Hyperhomocysteinemia Induces Vascular Remodeling During Atherosclerosis in Pon1 Knockout Mice

Background: Hyperhomocysteinemia (HHcy) is an independent risk factor for various cardiovascular diseases including hypertension, coronary artery disease and atherosclerosis. Previous studies have reported the anti-atherogenic properties of paraoxynase1 (PON1) through its homocysteine thiolactonase activity. Studies from our lab have shown abnormal matrix remodeling due to elevated MMP-9 expression, decreased vascular connexins (37 & 40) and endothelial dysfunction during HHcy. In the current study we examine the role of homocysteine and its effect on vascular remodeling during atherosclerosis in PON1 knockout mice. We hypothesize that PON1 knockout mice develop HHcy that induces MMP-9 expression and causes decreased Akt/ eNOS expression leading to vascular remodeling in atherosclerosis. Methods: PON1 knockout mice were fed on atherogenic diet for 15 weeks as atherosclerosis disease model and compared with C57BL/6J (wild type) controls. Blood pressure was measured by tail cuff method and cardiovascular fu...