Abstract
The objective of this study is to test the hypothesis that increased muscle mass has positive effects on cardiovascular function. Specifically, we tested the hypothesis that increases in lean body mass caused by deletion of myostatin improves cardiac performance and vascular function. Echocardiography was used to quantify left ventricular function at baseline and after acute administration of propranolol and isoproterenol to assess β‐adrenergic reactivity. Additionally, resistance vessels in several beds were removed, cannulated, pressurized to 60 mmHg and reactivity to vasoactive stimuli was assessed. Hemodynamics were measured using in vivo radiotelemetry. Myostatin deletion results in increased fractional shortening at baseline. Additionally, arterioles in the coronary and muscular microcirculations are more sensitive to endothelial‐dependent dilation while nonmuscular beds or the aorta were unaffected. β‐adrenergic dilation was increased in both coronary and conduit arteries, suggesting a systemic effect of increased muscle mass on vascular function. Overall hemodynamics and physical characteristics (heart weight and size) remained unchanged. Myostatin deletion mimics in part the effects of exercise on cardiovascular function. It significantly increases lean muscle mass and results in muscle‐specific increases in endothelium‐dependent vasodilation. This suggests that increases in muscle mass may serve as a buffer against pathological states that specifically target cardiac function (heart failure), the β‐adrenergic system (age), and nitric oxide bio‐availability (atherosclerosis). Taken together, pharmacological inhibition of the myostatin pathway could prove an excellent mechanism by which the benefits of exercise can be conferred in patients that are unable to exercise.
Highlights
The cardiovascular benefits of exercise are well characterized but a significant population in the United States is constrained by time, access, or preexisting conditions and unable to appropriately exercise, depriving them of these cardiometabolic improvements (Myers 2003; Lee et al 2012; Arem et al 2015; Carlson et al 2015; Gebel et al 2015)
Insulin and triglycerides were similar between the groups but plasma leptin was significantly reduced with myostatin deletion
Myostatin is a potent negative regulator of skeletal muscle growth and its therapeutic potential is of great interest in patients who are unable to adequately exercise
Summary
The cardiovascular benefits of exercise are well characterized but a significant population in the United States is constrained by time, access, or preexisting conditions and unable to appropriately exercise, depriving them of these cardiometabolic improvements (Myers 2003; Lee et al 2012; Arem et al 2015; Carlson et al 2015; Gebel et al 2015). Substantial effort has focused on understanding the key mechanisms that drive the cardiometabolic benefits of exercise, independent of physical activity (Matsakas and Diel 2005; Camporez et al 2016). One important aspect of exercise is increases in muscle size. A member of the TGF-b superfamily, has been identified as an important negative regulator of skeletal muscle mass (Matsakas and Diel 2005; Patel and Amthor 2005).
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