Deletion of myostatin improves cardiac and vascular function in mice.

Abstract

Exercise increases muscle mass but the cardiovascular benefits of increased muscle mass are controversial. The deletion of growth factor myostatin (Ms) increases muscle mass but the impact on cardiovascular function is unknown. The current study determined if cardiac (ultrasound) or coronary vascular (isolated arterioles) function were affected by myostatin deletion. On an ICR background, lean and Ms‐null mice were similar in body weight but Ms‐null mice displayed significantly lower visceral fat and plasma leptin levels. Fasting glucose and lipids were comparable between groups. Blood pressure and heart rate assessed by radiotelemetry were similar in control and Ms‐null mice. While heart mass, myocyte size and end diastolic diameter were similar between groups, deletion of Ms increased ejection fraction by 35% (27.9ƒn±1.0 vs. 37.4±1.9%). Ejection fraction in Ms‐null mice was increased during adrenergic stimulation (isoproteronol) and blockade (propranolol) in a parallel fashion. Maximal coronary dilation to ACh was increased by 25% in septal arterioles (63±2 vs. 51±4%, p<0.01). These data suggest that Ms deletion has salutary effects on cardiac physiology, increasing contractile and endothelial function. Without direct effects on cardiac mass, deletion of Ms may produce pre‐loaded heart, improving endothelial function secondary to increased perfusion. (NIH HL76533 and 92447).