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

5 Citations (Scopus)

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 1 2017

Fingerprint

Myostatin
Muscles
Adrenergic Agents
Exercise
Blood Vessels
Dilatation
Hemodynamics
Arterioles
Microcirculation
Left Ventricular Function
Isoproterenol
Vasodilation
Propranolol
Endothelium
Echocardiography
Aorta
Atherosclerosis
Coronary Vessels
Buffers
Nitric Oxide

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Butcher, J. T., Ali, M. I., Ma, M. W., McCarthy, C. G., Islam, B. N., Fox, L. G., ... 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

Effect of myostatin deletion on cardiac and microvascular function. / 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.

In: Physiological reports, Vol. 5, No. 23, e13525, 01.12.2017.

Research output: Contribution to journalArticle

Butcher, JT, Ali, MI, Ma, MW, McCarthy, CG, Islam, BN, Fox, LG, Mintz, JD, Larion, S, Fulton, DJ & Stepp, DW 2017, 'Effect of myostatin deletion on cardiac and microvascular function', Physiological reports, vol. 5, no. 23, e13525. https://doi.org/10.14814/phy2.13525
Butcher JT, Ali MI, Ma MW, McCarthy CG, Islam BN, Fox LG et al. Effect of myostatin deletion on cardiac and microvascular function. Physiological reports. 2017 Dec 1;5(23). e13525. https://doi.org/10.14814/phy2.13525
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. / Effect of myostatin deletion on cardiac and microvascular function. In: Physiological reports. 2017 ; Vol. 5, No. 23.
@article{7c699a3534c64230b1b8fc7ad79c242b,
title = "Effect of myostatin deletion on cardiac and microvascular function",
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.",
keywords = "Augmented muscle mass, Cardiac function, Coronary microvasculature, Exercise, Myostatin, Nitric oxide, β-adrenergic",
author = "Butcher, {Joshua T.} and Ali, {M. Irfan} and Ma, {Merry W.} and McCarthy, {Cameron G.} and Islam, {Bianca N.} and Fox, {Lauren G.} and Mintz, {James D.} and Sebastian Larion and Fulton, {David J} and Stepp, {David W}",
year = "2017",
month = "12",
day = "1",
doi = "10.14814/phy2.13525",
language = "English (US)",
volume = "5",
journal = "Physiological Reports",
issn = "2051-817X",
publisher = "John Wiley and Sons Inc.",
number = "23",

}

TY - JOUR

T1 - Effect of myostatin deletion on cardiac and microvascular function

AU - Butcher, Joshua T.

AU - Ali, M. Irfan

AU - Ma, Merry W.

AU - McCarthy, Cameron G.

AU - Islam, Bianca N.

AU - Fox, Lauren G.

AU - Mintz, James D.

AU - Larion, Sebastian

AU - Fulton, David J

AU - Stepp, David W

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

KW - Augmented muscle mass

KW - Cardiac function

KW - Coronary microvasculature

KW - Exercise

KW - Myostatin

KW - Nitric oxide

KW - β-adrenergic

UR - http://www.scopus.com/inward/record.url?scp=85037612646&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85037612646&partnerID=8YFLogxK

U2 - 10.14814/phy2.13525

DO - 10.14814/phy2.13525

M3 - Article

VL - 5

JO - Physiological Reports

JF - Physiological Reports

SN - 2051-817X

IS - 23

M1 - e13525

ER -