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Differential morphofunctional characteristics and gene expression in fast and slow muscle of rats with monocrotaline-induced heart failure.

Abstract
Heart failure (HF) is characterized by limited exercise tolerance, skeletal muscle atrophy, a shift toward fast muscle fiber, and myogenic regulatory factor (MRF) changes. Reactive oxygen species (ROS) also contribute to target organ damage in this syndrome. In this study, we investigated and compared morphofunctional characteristics and gene expression in Soleus (SOL--oxidative and slow twitching muscle) and in Extensor Digitorum Longus (EDL--glycolytic and fast twitching muscle) during HF. Two groups of rats were used: control (CT) and heart failure (HF), induced by a single injection of monocrotaline. MyoD and myogenin gene expression were determined by RT-qPCR, and MHC isoforms by SDS-PAGE; muscle fiber type frequency and cross sectional area (CSA) were analyzed by mATPase. A biochemical study was performed to determine lipid hydroperoxide (LH), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD); myography was used to determine amplitude, rise time, fall time, and fatigue resistance in both muscles. HF showed SOL and EDL muscle atrophy in all muscle fiber types; fiber frequency decreased in type IIC and muscle contraction fall time increased only in SOL muscle. Myogenin mRNA expression was lower in SOL and myoD decreased in HF EDL muscle. LH increased, and SOD and GSH-Px activity decreased only in HF SOL muscle. HF EDL muscle did not present changes in MHC distribution, contractile properties, HL concentration, and antioxidant enzyme activity. In conclusion, our results indicate that monocrotaline induced HF promoted more prominent biochemical, morphological and functional changes in SOL (oxidative and slow twitching muscle). Although further experiments are required to better determine the mechanisms involved in HF pathophysiology, our results contribute to understanding the muscle-specific changes that occur in this syndrome.
AuthorsRaquel Santilone Bertaglia, Joyce Reissler, Francis Silva Lopes, Walter Luiz Garrido Cavalcante, Fernanda Regina Carani, Carlos Roberto Padovani, Sergio Augusto Rodrigues, Antônio Carlos Cigogna, Robson Francisco Carvalho, Ana Angélica Henrique Fernandes, Marcia Gallacci, Maeli Dal Pai Silva
JournalJournal of molecular histology (J Mol Histol) Vol. 42 Issue 3 Pg. 205-15 (Jun 2011) ISSN: 1567-2387 [Electronic] Netherlands
PMID21509445 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • MyoD Protein
  • Myogenin
  • RNA, Messenger
  • Monocrotaline
Topics
  • Animals
  • Gene Expression Regulation
  • Heart Failure (chemically induced, physiopathology)
  • Male
  • Monocrotaline
  • Muscle Contraction (physiology)
  • Muscle Fibers, Fast-Twitch (metabolism, pathology)
  • Muscle Fibers, Slow-Twitch (metabolism, pathology)
  • Muscular Atrophy (metabolism, pathology)
  • MyoD Protein (genetics)
  • Myogenin (genetics)
  • RNA, Messenger (genetics)
  • Rats
  • Rats, Wistar

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