Glypican‐1 Plays a Cardiac Protective Effect During Heart Failure Induced by Pressure Overload

Abstract

About 1 in every 4 deaths is due to heart disease. Specifically, heart failure in its different forms impacts about 5.7 million people in the U.S. Hemodynamic pressure overload is a known cause for heart dysfunction and it may culminate in heart failure. Glypican‐1 (Gpc1) is a heparan sulfate proteoglycan that has mechanosensitive properties. Its role on heart function is not well understood but it may play a role on cardiac response to increased pressure. Herein we sought to investigate if deletion of Gpc1 contributes to cardiac dysfunction in a model of heart failure induced by pressure overload (Transverse Aortic Constriction, TAC). CD1 (wild type, WT) and Gpc1 knockout (Gpc1KO) mice were submitted to either a sham or TAC procedure. Heart function was assessed by echocardiography (ECHO) before (baseline), three and five weeks post‐surgery. The parameters analyzed by the ECHO were: stroke volume, cardiac output, left ventricle mass, left ventricle anterior wall during diastole (LVAWd), left ventricle posterior wall during diastole (LVPWd), left ventricle mean wall thickness (WTd), eccentricity, heart rate and ejection fraction. Baseline ejection fraction and heart rate was similar between WT and Gpc1KO. Baseline stroke volume, cardiac output and WTd were increased whereas eccentricity was decreased in Gpc1KO. Gpc1KO showed increased susceptibility to heart failure as evidenced by a faster and steep decrease in ejection fraction when compared to WT. In addition, Gpc1KO uniquely showed decreased stroke volume and cardiac output after 5 weeks of TAC. Left ventricle size was increased and eccentricity was decreased in the same time‐frame for both lines. Taken together, these results indicate that Gpc1 has a protective effect on cardiac function in a model of heart failure caused by pressure overload.Support or Funding InformationDepartment of Anesthesiology, College of Medicine, Tucson