Effect of myostatin deletion on cardiac and microvascular function. Issue 23 (30th November 2017)

• Record Type: Journal Article
• Authors: Butcher, Joshua T.; Ali, M. Irfan; Ma, Merry W.; McCarthy, Cameron G.; Islam, Bianca N.; Fox, Lauren G.; Mintz, James D.; Larion, Sebastian; Fulton, David J.; Stepp, David W.
• Is Part Of: Physiological reports. Volume 5:Issue 23(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-11-30
• Subjects: Augmented muscle mass -- cardiac function -- coronary microvasculature -- exercise -- myostatin -- nitric oxide -- β‐adrenergic; Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.13525
• Languages: English
• ISSNs: 2051-817X

Abstract

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. Abstract : While exercise is known to impact cardiovascular function, the effects of increased muscle mass as commonly seen in exercise is unknown. Using deletion of myostatin to augment muscle mass, we find increased cardiac function and heightened vasodlation, independent of physical activity. These data suggest that muscle mass as an independent variable can explain in part some of the effects of exercise.