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Increasing Muscle Mass Improves Vascular Function in Obese (db/db) Mice

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 vascu...

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Autores principales: Qiu, Shuiqing, Mintz, James D., Salet, Christina D., Han, Weihong, Giannis, Athanassios, Chen, Feng, Yu, Yanfang, Su, Yunchao, Fulton, David J., Stepp, David W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309080/
https://www.ncbi.nlm.nih.gov/pubmed/24965025
http://dx.doi.org/10.1161/JAHA.114.000854
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author Qiu, Shuiqing
Mintz, James D.
Salet, Christina D.
Han, Weihong
Giannis, Athanassios
Chen, Feng
Yu, Yanfang
Su, Yunchao
Fulton, David J.
Stepp, David W.
author_facet Qiu, Shuiqing
Mintz, James D.
Salet, Christina D.
Han, Weihong
Giannis, Athanassios
Chen, Feng
Yu, Yanfang
Su, Yunchao
Fulton, David J.
Stepp, David W.
author_sort Qiu, Shuiqing
collection PubMed
description 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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spelling pubmed-43090802015-01-28 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. J Am Heart Assoc Original Research 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. Blackwell Publishing Ltd 2014-06-25 /pmc/articles/PMC4309080/ /pubmed/24965025 http://dx.doi.org/10.1161/JAHA.114.000854 Text en © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/3.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Research
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
title Increasing Muscle Mass Improves Vascular Function in Obese (db/db) Mice
title_full Increasing Muscle Mass Improves Vascular Function in Obese (db/db) Mice
title_fullStr Increasing Muscle Mass Improves Vascular Function in Obese (db/db) Mice
title_full_unstemmed Increasing Muscle Mass Improves Vascular Function in Obese (db/db) Mice
title_short Increasing Muscle Mass Improves Vascular Function in Obese (db/db) Mice
title_sort increasing muscle mass improves vascular function in obese (db/db) mice
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309080/
https://www.ncbi.nlm.nih.gov/pubmed/24965025
http://dx.doi.org/10.1161/JAHA.114.000854
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