Skeletal muscle molecular alterations precede whole-muscle dysfunction in NYHA Class II heart failure patients

Michael P Godard,1 Samantha A Whitman,2 Yao-Hua Song,3 Patrice Delafontaine41Department of Nutrition and Kinesiology, University of Central Missouri, Warrensburg, MO, USA; 2Department of Cell Biology and Anatomy, University of Arizona, Tucson, AZ, USA; 3Cyrus Tang Hematology Center, Jiangsu Institut...

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Autores principales:	Godard MP, Whitman SA, Song YH, Delafontaine P
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Skeletal Muscle Heart Failure mRNA Geriatrics RC952-954.6
Acceso en línea:	https://doaj.org/article/81c7591ce4ed4ad780f4e106d6331e5f
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spelling	oai:doaj.org-article:81c7591ce4ed4ad780f4e106d6331e5f2021-12-02T06:10:28ZSkeletal muscle molecular alterations precede whole-muscle dysfunction in NYHA Class II heart failure patients1178-1998https://doaj.org/article/81c7591ce4ed4ad780f4e106d6331e5f2012-11-01T00:00:00Zhttps://www.dovepress.com/skeletal-muscle-molecular-alterations-precede-whole-muscle-dysfunction-peer-reviewed-article-CIAhttps://doaj.org/toc/1178-1998Michael P Godard,1 Samantha A Whitman,2 Yao-Hua Song,3 Patrice Delafontaine41Department of Nutrition and Kinesiology, University of Central Missouri, Warrensburg, MO, USA; 2Department of Cell Biology and Anatomy, University of Arizona, Tucson, AZ, USA; 3Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, Suzhou, China; 4Tulane University School of Medicine, Section of Cardiology, New Orleans, LA, USABackground: Heart failure (HF), a debilitating disease in a growing number of adults, exerts structural and neurohormonal changes in both cardiac and skeletal muscles. However, these alterations and their affected molecular pathways remain uncharacterized. Disease progression is known to transform skeletal muscle fiber composition by unknown mechanisms. In addition, perturbation of specific hormonal pathways, including those involving skeletal muscle insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-5 (IGFB-5) appears to occur, likely affecting muscle metabolism and regeneration. We hypothesized that changes in IGF-1 and IGFB-5 mRNA levels correlate with the transformation of single–skeletal muscle fiber myosin heavy chain isoforms early in disease progression, making these molecules valuable markers of skeletal muscle changes in heart failure.Materials and methods: To investigate these molecules during “early” events in HF patients, we obtained skeletal muscle biopsies from New York Heart Association (NYHA) Class II HF patients and controls for molecular analyses of single fibers, and we also quantified isometric strength and muscle size.Results: There were more (P < 0.05) single muscle fibers coexpressing two or more myosin heavy chains in the HF patients (30% ± 7%) compared to the control subjects (13% ± 2%). IGF-1 and IGFBP-5 expression was fivefold and 15-fold lower in patients with in HF compared to control subjects (P < 0.05), respectively. Strikingly, there was a correlation in IGF-1 expression and muscle cross-sectional area (P < 0.05) resulting in a decrease in whole-muscle quality (P < 0.05) in the HF patients, despite no significant decrease in isometric strength or whole-muscle size.Conclusion: These data indicate that molecular alterations in myosin heavy chain isoforms, IGF-1, and IGFB-5 levels precede the gross morphological and functional deficits that have previously been associated with HF, and may be used as a predictor of functional outcome in patients.Keywords: muscle quality, hybrid fibers, IGF1 and IGFBP-5Godard MPWhitman SASong YHDelafontaine PDove Medical PressarticleSkeletal MuscleHeart FailuremRNAGeriatricsRC952-954.6ENClinical Interventions in Aging, Vol Volume 7, Pp 489-497 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Skeletal Muscle Heart Failure mRNA Geriatrics RC952-954.6
spellingShingle	Skeletal Muscle Heart Failure mRNA Geriatrics RC952-954.6 Godard MP Whitman SA Song YH Delafontaine P Skeletal muscle molecular alterations precede whole-muscle dysfunction in NYHA Class II heart failure patients
description	Michael P Godard,1 Samantha A Whitman,2 Yao-Hua Song,3 Patrice Delafontaine41Department of Nutrition and Kinesiology, University of Central Missouri, Warrensburg, MO, USA; 2Department of Cell Biology and Anatomy, University of Arizona, Tucson, AZ, USA; 3Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, Suzhou, China; 4Tulane University School of Medicine, Section of Cardiology, New Orleans, LA, USABackground: Heart failure (HF), a debilitating disease in a growing number of adults, exerts structural and neurohormonal changes in both cardiac and skeletal muscles. However, these alterations and their affected molecular pathways remain uncharacterized. Disease progression is known to transform skeletal muscle fiber composition by unknown mechanisms. In addition, perturbation of specific hormonal pathways, including those involving skeletal muscle insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-5 (IGFB-5) appears to occur, likely affecting muscle metabolism and regeneration. We hypothesized that changes in IGF-1 and IGFB-5 mRNA levels correlate with the transformation of single–skeletal muscle fiber myosin heavy chain isoforms early in disease progression, making these molecules valuable markers of skeletal muscle changes in heart failure.Materials and methods: To investigate these molecules during “early” events in HF patients, we obtained skeletal muscle biopsies from New York Heart Association (NYHA) Class II HF patients and controls for molecular analyses of single fibers, and we also quantified isometric strength and muscle size.Results: There were more (P < 0.05) single muscle fibers coexpressing two or more myosin heavy chains in the HF patients (30% ± 7%) compared to the control subjects (13% ± 2%). IGF-1 and IGFBP-5 expression was fivefold and 15-fold lower in patients with in HF compared to control subjects (P < 0.05), respectively. Strikingly, there was a correlation in IGF-1 expression and muscle cross-sectional area (P < 0.05) resulting in a decrease in whole-muscle quality (P < 0.05) in the HF patients, despite no significant decrease in isometric strength or whole-muscle size.Conclusion: These data indicate that molecular alterations in myosin heavy chain isoforms, IGF-1, and IGFB-5 levels precede the gross morphological and functional deficits that have previously been associated with HF, and may be used as a predictor of functional outcome in patients.Keywords: muscle quality, hybrid fibers, IGF1 and IGFBP-5
format	article
author	Godard MP Whitman SA Song YH Delafontaine P
author_facet	Godard MP Whitman SA Song YH Delafontaine P
author_sort	Godard MP
title	Skeletal muscle molecular alterations precede whole-muscle dysfunction in NYHA Class II heart failure patients
title_short	Skeletal muscle molecular alterations precede whole-muscle dysfunction in NYHA Class II heart failure patients
title_full	Skeletal muscle molecular alterations precede whole-muscle dysfunction in NYHA Class II heart failure patients
title_fullStr	Skeletal muscle molecular alterations precede whole-muscle dysfunction in NYHA Class II heart failure patients
title_full_unstemmed	Skeletal muscle molecular alterations precede whole-muscle dysfunction in NYHA Class II heart failure patients
title_sort	skeletal muscle molecular alterations precede whole-muscle dysfunction in nyha class ii heart failure patients
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/81c7591ce4ed4ad780f4e106d6331e5f
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Skeletal muscle molecular alterations precede whole-muscle dysfunction in NYHA Class II heart failure patients

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