Cardiomyocyte hypertrophy co-localizes with accumulation of hyaluronan in cMyBPC+/- mice hearts

Abstract

Hypertrophic cardiomyopathy (HCM) is a genetic heart disease characterized by left ventricular hypertrophy. Mutations in genes for sarcomere proteins, e.g. in cardiac myosin-binding protein C (cMyBPC), cause symptoms like heart failure and sudden cardiac death. In HCM, the heart utilizes high amounts of glucose. Increased glucose metabolism creates intermediates for hyaluronan (HA) synthesis, resulting in HA accumulation within the extracellular space, which could contribute to cardiomyocyte hypertrophy. We aimed to describe the connection between HA and cardiomyocyte hypertrophy using cMyBPC+/- mice treated with two different {beta}-blockers - either metoprolol or propranolol - for 11 months. The results showed that HA metabolism is altered in HCM, and consequently, HA is significantly more abundant in hearts of cMyBPC+/- mice compared to wild-type mice. High HA abundance correlated with increased cardiomyocyte size. Gene expression of HA synthase 2 was elevated in cMyBPC+/- mice. Treatment with propranolol significantly increased HA synthase 3 expression, while HA synthase 2 was maintained at wild-type level. Treatment with metoprolol or propranolol did not prevent HA accumulation nor decreased cardiomyocyte hypertrophy. These findings show a novel connection between high HA abundance and cardiomyocyte hypertrophy in cMyBPC+/- mice.