Abstract 514: Endothelial Cell-Specific Molecule 1 or Endocan Is Required for Postnatal Cardiac Function

Abstract

Introduction: Endothelial specific molecule 1 (ESM1) or Endocan is an endothelial secreted dermatan sulphate proteoglycan whose function remains elusive. ESM-1 is detected at a level of approximately 1 ng/ml in the plasma of healthy individuals and is significantly elevated in diseased states like cancer and sepsis. ESM1 expression in vivo is limited while its expression is up regulated in tumor neovessels. However there have been no in vivo studies of ESM1 function to date. Objective: The aim of this study was to understand the function of ESM1 in vivo using a global ESM1 knockout (KO) mouse model. Methods and results: ESM1 KO mice were generated by deleting the exon 1 containing the coding region of the mouse gene. Mice were backcrossed in C57BL/6 background for more than 10 generations. Targeted deletion of ESM1 was confirmed by real time quantitative RT-PCR (qRT-PCR). Analysis of ESM1 KO embryos and yolk sac at different time points (E12.5, E15.5) showed normal vasculature compared to WT controls. ESM1 KO mice were born at the normal mendelian but they showed 50% perinatal mortality by postnatal day 3 (P3). Pathological analysis of mice that died at P2 revealed dilated atria engorged with blood and thrombi indicative of possible defect in cardiac contractility. Pulmonary congestion was also observed indicative of possible cardiac failure. Fetal genes associated with cardiac stress response including atrial natriuretic peptide (Nppa), brain natriuretic pepetide (Nppb) and beta-myosin heavy chain (Myh7) were significantly up regulated in ESM1 KO postnatal (P2) hearts compared to controls. Conclusion: Our findings demonstrate for the first time that ESM1 is required for postnatal cardiac function. Future studies are aimed at understanding the mechanisms leading to impaired cardiac function in ESM1 KO mice.