Increasing muscle mass improves vascular function in obese (DB/DB) Mice

Shuiqing Qiu, James D. Mintz, Christina D. Salet, Weihong Han, Athanassios Giannis, Feng Chen, Yanfang Yu, Yunchao Su, David J Fulton, David W Stepp

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: A sedentary lifestyle is an independent risk factor for cardiovascular disease and exercise has been shown to ameliorate this risk. Inactivity is associated with a loss of muscle mass, which is also reversed with isometric exercise training. The relationship between muscle mass and vascular function is poorly defined. The aims of the current study were to determine whether increasing muscle mass by genetic deletion of myostatin, a negative regulator of muscle growth, can influence vascular function in mesenteric arteries from obese db/db mice. Methods and Results: Myostatin expression was elevated in skeletal muscle of obese mice and associated with reduced muscle mass (30% to 50%). Myostatin deletion increased muscle mass in lean (40% to 60%) and obese (80% to 115%) mice through increased muscle fiber size (P<0.05). Myostatin deletion decreased adipose tissue in lean mice, but not obese mice. Markers of insulin resistance and glucose tolerance were improved in obese myostatin knockout mice. Obese mice demonstrated an impaired endothelial vasodilation, compared to lean mice. This impairment was improved by superoxide dismutase mimic Tempol. Deletion of myostatin improved endothelial vasodilation in mesenteric arteries in obese, but not in lean, mice. This improvement was blunted by nitric oxide (NO) synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME). Prostacyclin (PGI 2 )- and endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilation were preserved in obese mice and unaffected by myostatin deletion. Reactive oxygen species) was elevated in the mesenteric endothelium of obese mice and down-regulated by deletion of myostatin in obese mice. Impaired vasodilation in obese mice was improved by NADPH oxidase inhibitor (GKT136901). Treatment with sepiapterin, which increases levels of tetrahydrobiopterin, improved vasodilation in obese mice, an improvement blocked by L-NAME. Conclusions: Increasing muscle mass by genetic deletion of myostatin improves NO-, but not PGI 2 - or EDHF-mediated vasodilation in obese mice; this vasodilation improvement is mediated by down-regulation of superoxide.

Original languageEnglish (US)
Article number000854
JournalJournal of the American Heart Association
Volume3
Issue number3
DOIs
StatePublished - Jan 1 2014

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Myostatin
Obese Mice
Blood Vessels
Vasodilation
Muscles
Endothelium
Mesenteric Arteries
NG-Nitroarginine Methyl Ester
Exercise
Sedentary Lifestyle
NADPH Oxidase
Epoprostenol
Knockout Mice
Nitric Oxide Synthase
Superoxides
Superoxide Dismutase
Insulin Resistance
Adipose Tissue
Reactive Oxygen Species
Nitric Oxide

Keywords

  • Muscle mass
  • Myostatin
  • NOX1
  • Oxidant stress
  • Tetrahydrobiopterin
  • Vasodilation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Increasing muscle mass improves vascular function in obese (DB/DB) Mice. / Qiu, Shuiqing; Mintz, James D.; Salet, Christina D.; Han, Weihong; Giannis, Athanassios; Chen, Feng; Yu, Yanfang; Su, Yunchao; Fulton, David J; Stepp, David W.

In: Journal of the American Heart Association, Vol. 3, No. 3, 000854, 01.01.2014.

Research output: Contribution to journalArticle

Qiu, Shuiqing ; Mintz, James D. ; Salet, Christina D. ; Han, Weihong ; Giannis, Athanassios ; Chen, Feng ; Yu, Yanfang ; Su, Yunchao ; Fulton, David J ; Stepp, David W. / Increasing muscle mass improves vascular function in obese (DB/DB) Mice. In: Journal of the American Heart Association. 2014 ; Vol. 3, No. 3.
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AU - Giannis, Athanassios

AU - Chen, Feng

AU - Yu, Yanfang

AU - Su, Yunchao

AU - Fulton, David J

AU - Stepp, David W

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N2 - Background: A sedentary lifestyle is an independent risk factor for cardiovascular disease and exercise has been shown to ameliorate this risk. Inactivity is associated with a loss of muscle mass, which is also reversed with isometric exercise training. The relationship between muscle mass and vascular function is poorly defined. The aims of the current study were to determine whether increasing muscle mass by genetic deletion of myostatin, a negative regulator of muscle growth, can influence vascular function in mesenteric arteries from obese db/db mice. Methods and Results: Myostatin expression was elevated in skeletal muscle of obese mice and associated with reduced muscle mass (30% to 50%). Myostatin deletion increased muscle mass in lean (40% to 60%) and obese (80% to 115%) mice through increased muscle fiber size (P<0.05). Myostatin deletion decreased adipose tissue in lean mice, but not obese mice. Markers of insulin resistance and glucose tolerance were improved in obese myostatin knockout mice. Obese mice demonstrated an impaired endothelial vasodilation, compared to lean mice. This impairment was improved by superoxide dismutase mimic Tempol. Deletion of myostatin improved endothelial vasodilation in mesenteric arteries in obese, but not in lean, mice. This improvement was blunted by nitric oxide (NO) synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME). Prostacyclin (PGI 2 )- and endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilation were preserved in obese mice and unaffected by myostatin deletion. Reactive oxygen species) was elevated in the mesenteric endothelium of obese mice and down-regulated by deletion of myostatin in obese mice. Impaired vasodilation in obese mice was improved by NADPH oxidase inhibitor (GKT136901). Treatment with sepiapterin, which increases levels of tetrahydrobiopterin, improved vasodilation in obese mice, an improvement blocked by L-NAME. Conclusions: Increasing muscle mass by genetic deletion of myostatin improves NO-, but not PGI 2 - or EDHF-mediated vasodilation in obese mice; this vasodilation improvement is mediated by down-regulation of superoxide.

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