Abstract WP311: Bilateral Common Carotid Artery Stenosis Induces Cardiac Dysfunction in Mice Which is Exacerbated in Mice Deficient in Endothelial Nitric Oxide Synthase

Abstract

Background: We investigated whether bilateral common carotid artery stenosis (BCAS) induces cardiac dysfunction in the absence of primary cardiac disease in mice, and whether deficiency of endothelial nitric oxide synthase (eNOS) exacerbates cardiac dysfunction in mice subjected to BCAS. Methods: Male, middle-aged (6-8 month), wild type (WT) and eNOS knockout (eNOS-/-) mice were subjected to sham surgery or BCAS using microcoils (0.16mm internal diameter)(n=6 per group). Cardiac function was measured at day 30 after surgery using echocardiography. Immunostaining was employed to assess inflammatory factor expression in the heart. Results: 1) Compared to WT-control mice, WT-BCAS mice exhibited significant cardiac dysfunction identified by decreased Left Ventricular Ejection Fraction (LVEF) and Ventricular Ejection Fractional Shortening (LVFS), increased cardiomyocyte apoptosis and CD45+ inflammatory cell infiltration.2) Compared to WT-BCAS mice, eNOS-/-BCAS mice exhibited significantly exacerbated cardiac dysfunction identified by decreasing LVFS, increased CD45+ inflammatory cell infiltration into heart tissue, and decreased CD206+ anti-inflammatory cell expression in the heart. Conclusions: BCAS induces cardiac dysfunction in the absence of primary cardiac disease in mice, and mice deficient of eNOS subjected to BCAS exhibit exacerbated cardiac dysfunction and inflammatory factor expression.