Abstract 14412: Endothelial Cell-Selective Adhesion Molecule Deficiency in Mice Causes Vascular Endothelial Dysfunction and Impairs Left Ventricle Diastolic Function

Abstract

Dysfunction of vascular endothelium plays a key role in the development of left ventricular diastolic dysfunction (LVDD) in patients with heart failure with preserved left ventricular ejection fraction (HFpEF). Recently, Endothelial Cell-Selective Adhesion Molecule (ESAM) was proposed as a novel biomarker in HFpEF. We hypothesized that ESAM plays a mechanistic role in the development of both microvascular dysfunction and LVDD. ESAM knockout and wild type (WT) mice were employed. Using transthoracic echocardiography it was found that ESAM knockout mice displayed LV diastolic dysfunction, as indicated by a significantly reduced E/A ratio (E=early, A=late mitral inflow peak velocities), increased E/e’ ratio, isovolumic relaxation time (IVRT) and increased E wave deceleration time, with no change in the ejection fraction. The systolic blood pressure, as measured by tail-cuff plethysmography, was not different between ESAM knockout and WT mice; and no cardiac hypertrophy was detected in the ESAM knockout mice. Vasodilator function of the pulmonary artery and aorta was assessed using wire myography. We found that the endothelium-dependent, acetylcholine-induced relaxation of the aorta and pulmonary artery was significantly reduced in ESAM knockout mice, whereas endothelium-independent, nitric oxide donor, sodium nitroprusside-induced relaxation was similar in the two groups. Thus, we concluded that ESAM deficiency in mice display a HFpEF phenotype, in that ESAM knockout mice develop endothelial dysfunction and LVDD.