Effect of myostatin deletion on cardiac and microvascular function

Joshua T. Butcher, M. Irfan Ali, Merry W. Ma, Cameron G. McCarthy, Bianca N. Islam, Lauren G. Fox, James D. Mintz, Sebastian Larion, David J Fulton, David W Stepp

Research output: Contribution to journalArticle

8 Scopus citations

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 endothe-lial-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.

Original languageEnglish (US)
Article numbere13525
JournalPhysiological reports
Volume5
Issue number23
DOIs
StatePublished - Dec 2017

Keywords

  • Augmented muscle mass
  • Cardiac function
  • Coronary microvasculature
  • Exercise
  • Myostatin
  • Nitric oxide
  • β-adrenergic

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Effect of myostatin deletion on cardiac and microvascular function'. Together they form a unique fingerprint.

  • Cite this

    Butcher, J. T., Ali, M. I., Ma, M. W., McCarthy, C. G., Islam, B. N., Fox, L. G., Mintz, J. D., Larion, S., Fulton, D. J., & Stepp, D. W. (2017). Effect of myostatin deletion on cardiac and microvascular function. Physiological reports, 5(23), [e13525]. https://doi.org/10.14814/phy2.13525