Changes in myofilament proteins, but not Ca²⁺ regulation, are associated with a high-fat diet-induced improvement in contractile function in heart failure

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 301; no. 4; p. H1438
• Main Authors: Cheng, Y, Li, W, McElfresh, T A, Chen, X, Berthiaume, J M, Castel, L, Yu, X, Van Wagoner, D R, Chandler, M P
• Format: Journal Article
• Language: English
• Published: United States 01-10-2011
• Subjects: Animals; Blotting, Western; Body Weight - physiology; Calcium - physiology; Calcium Channels, L-Type - physiology; Calcium Signaling - physiology; Coronary Vessels - physiology; Diet; Dietary Fats - pharmacology; Electrocardiography; Heart Failure - physiopathology; Hemodynamics - physiology; Ligation; Male; Myocardial Contraction - drug effects; Myocardium - metabolism; Myocardium - pathology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - physiology; Myofibrils - metabolism; Myosin Heavy Chains - metabolism; Phosphorylation; Rats; Rats, Wistar
• ISSN: 1522-1539
• DOI: 10.1152/ajpheart.00440.2011

Pathological conditions such as diabetes, insulin resistance, and obesity are characterized by elevated plasma and myocardial lipid levels and have been reported to exacerbate the progression of heart failure (HF). Alterations in cardiomyocyte Ca(2+) regulatory properties and myofilament proteins have also been implicated in contractile dysfunction in HF. However, our prior studies reported that high saturated fat (SAT) feeding improves in vivo myocardial contractile function, thereby exerting a cardioprotective effect in HF. Therefore, we hypothesized that SAT feeding improves contractile function by altering Ca(2+) regulatory properties and myofilament protein expression in HF. Male Wistar rats underwent coronary artery ligation (HF) or sham surgery (SH) and were fed normal chow (SHNC and HFNC groups) or a SAT diet (SHSAT and HFSAT groups) for 8 wk. Contractile properties were measured in vivo [echocardiography and left ventricular (LV) cannulation] and in isolated LV cardiomyocytes. In vivo measures of contractility (peak LV +dP/dt and -dP/dt) were depressed in the HFNC versus SHNC group but improved in the HFSAT group. Isolated cardiomyocytes from both HF groups were hypertrophied and had decreased percent cell shortening and a prolonged time to half-decay of the Ca(2+) transient versus the SH group; however, SAT feeding reduced in vivo myocyte hypertrophy in the HFSAT group only. The peak velocity of cell shortening was reduced in the HFNC group but not the HFSAT group and was positively correlated with in vivo contractile function (peak LV +dP/dt). The HFNC group demonstrated a myosin heavy chain (MHC) isoform switch from fast MHC-α to slow MHC-β, which was prevented in the HFSAT group. Alterations in Ca(2+) transients, L-type Ca(2+) currents, and protein expression of sarco(endo)plasmic reticulum Ca(2+)-ATPase and phosphorylated phospholamban could not account for the changes in the in vivo contractile properties. In conclusion, the cardioprotective effects associated with SAT feeding in HF may occur at the level of the isolated cardiomyocyte, specifically involving changes in myofilament function but not sarcoplasmic reticulum Ca(2+) regulatory properties.