Abstract P2048: New Insights Into The Role Of The Glycocalyx Components In Heart Failure Induced By Pressure Overload.

Abstract

Heart failure (HF) is a complex disease with multifactorial etiology. The degradation of the glycocalyx is a process thought to contribute to the progression of HF. The relative individual contribution of glycocalyx components to HF progression is unclear. Previous studies have shown that the expression of glypican 1 (Gpc1), a glycocalyx component, is reduced after aortic banding. Herein, we sought to determine if Gpc1 participates in the progression of HF induced by pressure overload and the associated mechanisms. Methods: Male, 5-8 weeks old, WT and Gpc1 knockout mice (Gpc1KO) were submitted to transaortic constriction (TAC) or sham procedure. Heart function was assessed by echocardiography; heart remodeling was assessed by histological analysis; heparan sulfate and glypican 1 content was assessed by immunofluorescence; the expression of ANP and myosin was assessed by immunoblotting. Results: Gpc1KO showed preserved heparan sulfate content in heart sections. Gpc1KO showed cardiac hypertrophy as evidenced by increased left ventricle mass (173.75mg vs. 123.96 mg in WT; p=0.004; n=10), left ventricle wall thickness (1.43mm vs . 1.13mm in WT; p=0.033; n=10), intraventricular septal end-diastolic thickness (1.83mm vs. 1.62mm in WT; p=0.001; n=11) and decreased cardiomyocyte cross-sectional area (203.86μm2 vs. 248.44μm2; p<0.0001; n=5). This was associated with increased stroke volume (52.89±2.1μL vs 46.42±2.0 μL; p=0.038, n=10), cardiac output (26.39 mL/min vs. 20.32 mL/min in WT), calcium deposits, ANP (0.86±0.02 vs. 0.57± 0.03; p<0.0001; n=5) and myosin (0.71±0.1 vs. 0.50±0.01 in WT; p=0.03; n=5) content in the heart. Gpc1KO were prone to TAC-induced HF as shown by decreased ejection fraction (34.37% vs . 58.41% in WT; p=0.047; n=3) and stroke volume (35.24μL vs. 44.60 μL in WT; p=0.05, n=3) 3 weeks after TAC. Moreover, Gpc1KO showed increased mortality rate, not surviving 5 weeks post-TAC. Conclusions: Gpc1KO shows basal cardiac remodeling associated with changes in calcium dynamics and increased contractility. The increased susceptibility of Gpc1KO to TAC-induced HF seems to be independent of glycocalyx degradation. Further studies are required to understand the mechanisms whereby Gpc1 regulates the progression of TAC-induced HF.