Alterations in myosin heavy chain and cell shortening velocity improve myocardial contractile function in high‐fat fed heart failure rats

Abstract

Elevations in plasma & myocardial lipids have been reported to exacerbate the progression of heart failure (HF). Alterations in cardiomyocyte Ca2+ handling are also implicated in the contractile dysfunction associated with HF. Previous studies have reported improved in vivo myocardial contractility with high fat feeding in HF, therefore we hypothesize that high fat feeding would improve cardiomyocyte Ca2+ handling and contractile properties in HF. Male rats underwent coronary ligation or sham surgery (SH) & fed normal (NC) or high saturated fat diet (SAT) for 8 weeks. In vivo measures of left ventricular (LV) contractility (peak +/−dP/dt) were depressed in HFNC vs. SHNC but improved in HFSAT. LV myocyte shortening velocity (−dL/dt) was diminished in HFNC vs. SHNC, but not in HFSAT. An increase in Ca2+ transients in HFNC vs. SHNC & HFSAT was accompanied by increased protein expression of sarcoplasmic reticulum Ca2+ ATPase & phosphorylated phospholamban. There was no difference in L-type Ca2+ currents, however HFNC demonstrated a myosin heavy chain (MHC) isoform switch from fast MHCα to slow MHCβ that was prevented in HFSAT. Myocyte cross sectional area was increased, indicating hypertrophy in HFNC, but decreased in HFSAT. In conclusion, changes in cell shortening velocity & MHCβ content may account for improvements in in vivo myocardial contractile function with high fat feeding in HF. (Grant: NHLBI HL-081857)