title: 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.
authors.affiliation: Department of Morphology, Institute of Biosciences, UNESP, São Paulo State University, 18618-000 Botucatu, SP, Brazil.
authors.forename: Raquel Santilone
authors.initials: RS
authors.lastname: Bertaglia
authors.forename: Joyce
authors.initials: J
authors.lastname: Reissler
authors.forename: Francis Silva
authors.initials: FS
authors.lastname: Lopes
authors.forename: Walter Luiz Garrido
authors.initials: WL
authors.lastname: Cavalcante
authors.forename: Fernanda Regina
authors.initials: FR
authors.lastname: Carani
authors.forename: Carlos Roberto
authors.initials: CR
authors.lastname: Padovani
authors.forename: Sergio Augusto
authors.initials: SA
authors.lastname: Rodrigues
authors.forename: Antônio Carlos
authors.initials: AC
authors.lastname: Cigogna
authors.forename: Robson Francisco
authors.initials: RF
authors.lastname: Carvalho
authors.forename: Ana Angélica Henrique
authors.initials: AA
authors.lastname: Fernandes
authors.forename: Marcia
authors.initials: M
authors.lastname: Gallacci
authors.forename: Maeli Dal Pai
authors.initials: MD
authors.lastname: Silva
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000139:chemically induced* / Q000503:physiopathology*; D008297:Male; D016686:Monocrotaline; D009119:Muscle Contraction / Q000502:physiology; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism* / Q000473:pathology; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000378:metabolism / Q000473:pathology; D017570:MyoD Protein / Q000235:genetics; D018008:Myogenin / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
chemical_list: D017570:MyoD Protein; D018008:Myogenin; D012333:RNA, Messenger; D016686:Monocrotaline