scholarly journals Transcriptome analysis of skeletal muscles revealed the effect of exercise on the molecular mechanisms regulating muscle growth and metabolism in patients with heart failure

2020 ◽  
Vol 25 (10) ◽  
pp. 4132
Author(s):  
O. A. Ivanova ◽  
E. V. Ignatieva ◽  
T. A. Lelyavina ◽  
V. L. Galenko ◽  
M. Yu. Komarova ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Skeletal Muscles ◽  
Molecular Mechanisms ◽  
Calcium Release ◽  
Exercise Program ◽  
Rehabilitation Program ◽  
Exercise Intolerance ◽  
Skeletal Muscle Atrophy ◽  
Muscle Membrane

Aim. Heart failure (HF) is accompanied by skeletal muscle atrophy and exercise intolerance. The aim was to study the molecular mechanisms underlying the therapeutic effect of personalized exercise in patients with HF.Material and methods. RNA sequencing obtained from skeletal muscle biopsies before and after a 12-week exercise course was used to identify changes in gene expression and signaling pathways induced by the physical rehabilitation program for patients with HF.Results. We have shown that personalized exercise program in patients with HF stimulates the activation of molecular pathways regulating the differentiation and functioning of skeletal muscles: commitment of muscle progenitor cells; mechanisms regulating the calcium release and sensitivity of myofibrillar contraction, electrical excitability of the muscle membrane, synaptic vesicle proton gradient creation, maintenance of electrochemical gradients of Na+ /K+ . Also, the analysis of differentially expressed genes revealed an increase in the expression of transcription factors MyoD and MEF2, which are responsible for the differentiation of muscle stem cells, and sarcomeric genes MYOM1, MYOM2, MYH7. Along with this, we observed activation of the CYR61 expression — a potential prognostic biomarker for HF patients.Conclusion. Our data show that the beneficial effect of personalized aerobic exercise in patients with HF depends, at least in part, on an improvement in the physiological and biochemical parameters of skeletal muscle.

scholarly journals Molecular background of impairments in skeletal muscle of heart failure patients

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
O Ivanova ◽  
M Y Komarova ◽  
E V Ignatieva ◽  
T A Lelyavina ◽  
V L Galenko ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Differentially Expressed Genes ◽  
Skeletal Muscles ◽  
Molecular Mechanisms ◽  
Class Ii ◽  
Differentially Expressed ◽  
Exercise Intolerance ◽  
Type I ◽  
Molecular Abnormalities

Abstract Background Heart failure (HF) is characterised by systematic inflammation and chronic metabolic dysregulation. HF enhances the release of pro-inflammatory cytokines, induces activation of the complement system, production of autoantibodies, and over-expression of the major histocompatibility (MHC) complex class II molecules. It is known that skeletal muscles are exposed to the immunologic injury in disease; and muscle tissue appeared to be affected by HF leading to the muscle weakness and exercise intolerance development. However, molecular abnormalities occurring in HF patients' muscles and the mechanisms underlying its development are not clarified. Purpose To understand the molecular mechanisms underlying skeletal muscle immune and non-immune impairments in HF. Methods 8 health donors and 5 HF patients with reduced ejection fraction (NYHA Class II and III) were enrolled in this study in accordance with the principles under the Declaration of Helsinki (1989). mRNA of skeletal muscle biopsies of gastrocnemius lateralis were sequenced on Illumina HiSeq. RNA-seq analysis was performed using STAR with reference genome GRCh38 and featureCounts program; differentially expressed genes (DEGs) were assessed using R package DESeq2 with FDR=0.01 and log2 fold change (l2fc) >1.5 filter; pathway analysis was performed using clusterProfiler in R (FDR=0.01). Results 1404 differentially expressed genes distinguish muscles of HF patients and controls. Among upregulated genes there are different classical MHC molecules and specific one HLA-G (l2fc=2) that has been previously shown appeared in muscles under autoimmune myopathies, and potentially protect them. Unregulated DEGs were responsible for the activation of many molecular immunological pathways: type I interferon signaling pathway (16 DEGs out of total 89), regulation of T cell proliferation (14/153), neutrophil degranulation (31/485), granulocyte differentiation (7/32), negative regulation of viral process (11/53), that indicates about specific inflammatory response in HF muscles. Response to hypoxia (22/314) and gluconeogenesis pathways (12/87) were also activated. Downregulated genes include SLC5A1 (l2fc=−4) sodium glucose cotransporter; NRP3 (l2fc=−4) that plays a role in modulating intravascular volume and vascular tone; MMP1 (l2fc=−13) involved in the breakdown of extracellular matrix; the expression of many genes responsible for DNA-repair (44/534) and cilium assembly (34/366) was also suppressed. Conclusion Transcriptome analysis shows immunological and non-immunological alterations in HF skeletal muscles and provides the information about molecular mechanisms of its development. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Russian Science Foundation grant

scholarly journals Skeletal muscle atrophy contributes to exercise intolerance in heart failure

1991 ◽  
Vol 17 (2) ◽  
pp. A88
Author(s):  
Donna M. Mancini ◽  
Deborah Nazzaro ◽  
Lynne Georgopoulos ◽  
Nancy Wagner ◽  
James L. Mullen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Exercise Intolerance ◽  
Skeletal Muscle Atrophy

scholarly journals Skeletal muscle atrophy in heart failure with diabetes: from molecular mechanisms to clinical evidence

2020 ◽  
Author(s):  
Nathanael Wood ◽  
Sam Straw ◽  
Mattia Scalabrin ◽  
Lee D. Roberts ◽  
Klaus K. Witte ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Molecular Mechanisms ◽  
Clinical Evidence ◽  
Skeletal Muscle Atrophy

scholarly journals Contribution of skeletal muscle atrophy to exercise intolerance and altered muscle metabolism in heart failure.

Circulation ◽  
1992 ◽  
Vol 85 (4) ◽  
pp. 1364-1373 ◽  
Author(s):  
D M Mancini ◽  
G Walter ◽  
N Reichek ◽  
R Lenkinski ◽  
K K McCully ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Muscle Metabolism ◽  
Exercise Intolerance ◽  
Skeletal Muscle Atrophy

scholarly journals Systemic oxidative stress is associated with lower aerobic capacity and impaired skeletal muscle energy metabolism in heart failure patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takashi Yokota ◽  
Shintaro Kinugawa ◽  
Kagami Hirabayashi ◽  
Mayumi Yamato ◽  
Shingo Takada ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Aerobic Capacity ◽  
Plantar Flexion ◽  
Exercise Intolerance ◽  
Whole Body ◽  
Resonance Spectroscopy ◽  
Systemic Oxidative Stress

AbstractOxidative stress plays a role in the progression of chronic heart failure (CHF). We investigated whether systemic oxidative stress is linked to exercise intolerance and skeletal muscle abnormalities in patients with CHF. We recruited 30 males: 17 CHF patients, 13 healthy controls. All participants underwent blood testing, cardiopulmonary exercise testing, and magnetic resonance spectroscopy (MRS). The serum thiobarbituric acid reactive substances (TBARS; lipid peroxides) were significantly higher (5.1 ± 1.1 vs. 3.4 ± 0.7 μmol/L, p < 0.01) and the serum activities of superoxide dismutase (SOD), an antioxidant, were significantly lower (9.2 ± 7.1 vs. 29.4 ± 9.7 units/L, p < 0.01) in the CHF cohort versus the controls. The oxygen uptake (VO2) at both peak exercise and anaerobic threshold was significantly depressed in the CHF patients; the parameters of aerobic capacity were inversely correlated with serum TBARS and positively correlated with serum SOD activity. The phosphocreatine loss during plantar-flexion exercise and intramyocellular lipid content in the participants' leg muscle measured by 31phosphorus- and 1proton-MRS, respectively, were significantly elevated in the CHF patients, indicating abnormal intramuscular energy metabolism. Notably, the skeletal muscle abnormalities were related to the enhanced systemic oxidative stress. Our analyses revealed that systemic oxidative stress is related to lowered whole-body aerobic capacity and skeletal muscle dysfunction in CHF patients.

scholarly journals Physiology of a Microgravity Environment Invited Review: Microgravity and skeletal muscle

2000 ◽  
Vol 89 (2) ◽  
pp. 823-839 ◽  
Author(s):  
Robert H. Fitts ◽  
Danny R. Riley ◽  
Jeffrey J. Widrick
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Thin Filament ◽  
Molecular Mechanisms ◽  
Skeletal Muscle Atrophy ◽  
Microgravity Environment ◽  
Type I ◽  
Fiber Types ◽  
Maximal Velocity ◽  
Cross Sectional

Spaceflight (SF) has been shown to cause skeletal muscle atrophy; a loss in force and power; and, in the first few weeks, a preferential atrophy of extensors over flexors. The atrophy primarily results from a reduced protein synthesis that is likely triggered by the removal of the antigravity load. Contractile proteins are lost out of proportion to other cellular proteins, and the actin thin filament is lost disproportionately to the myosin thick filament. The decline in contractile protein explains the decrease in force per cross-sectional area, whereas the thin-filament loss may explain the observed postflight increase in the maximal velocity of shortening in the type I and IIa fiber types. Importantly, the microgravity-induced decline in peak power is partially offset by the increased fiber velocity. Muscle velocity is further increased by the microgravity-induced expression of fast-type myosin isozymes in slow fibers (hybrid I/II fibers) and by the increased expression of fast type II fiber types. SF increases the susceptibility of skeletal muscle to damage, with the actual damage elicited during postflight reloading. Evidence in rats indicates that SF increases fatigability and reduces the capacity for fat oxidation in skeletal muscles. Future studies will be required to establish the cellular and molecular mechanisms of the SF-induced muscle atrophy and functional loss and to develop effective exercise countermeasures.

Soothing the sleeping giant: improving skeletal muscle oxygen kinetics and exercise intolerance in HFpEF

2015 ◽  
Vol 119 (6) ◽  
pp. 734-738 ◽  
Author(s):  
Satyam Sarma ◽  
Benjamin D. Levine
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Oxygen Consumption ◽  
Functional Capacity ◽  
Oxidative Capacity ◽  
Exercise Intolerance ◽  
Aerobic Performance ◽  
Muscle Oxygen ◽  
Oxygen Kinetics ◽  
Patients With Heart Failure

Patients with heart failure with preserved ejection fraction (HFpEF) have similar degrees of exercise intolerance and dyspnea as patients with heart failure with reduced EF (HFrEF). The underlying pathophysiology leading to impaired exertional ability in the HFpEF syndrome is not completely understood, and a growing body of evidence suggests “peripheral,” i.e., noncardiac, factors may play an important role. Changes in skeletal muscle function (decreased muscle mass, capillary density, mitochondrial volume, and phosphorylative capacity) are common findings in HFrEF. While cardiac failure and decreased cardiac reserve account for a large proportion of the decline in oxygen consumption in HFrEF, impaired oxygen diffusion and decreased skeletal muscle oxidative capacity can also hinder aerobic performance, functional capacity and oxygen consumption (V̇o2) kinetics. The impact of skeletal muscle dysfunction and abnormal oxidative capacity may be even more pronounced in HFpEF, a disease predominantly affecting the elderly and women, two demographic groups with a high prevalence of sarcopenia. In this review, we 1) describe the basic concepts of skeletal muscle oxygen kinetics and 2) evaluate evidence suggesting limitations in aerobic performance and functional capacity in HFpEF subjects may, in part, be due to alterations in skeletal muscle oxygen delivery and utilization. Improving oxygen kinetics with specific training regimens may improve exercise efficiency and reduce the tremendous burden imposed by skeletal muscle upon the cardiovascular system.

Metabolic Myopathy in Heart Failure

Physiology ◽  
2002 ◽  
Vol 17 (5) ◽  
pp. 191-196 ◽  
Author(s):  
Renée Ventura-Clapier ◽  
Elvira De Sousa ◽  
Vladimir Veksler
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Exercise Intolerance ◽  
Metabolic Myopathy

Heart failure is a syndrome that also affects the periphery. Exercise intolerance and early fatigue seem to be linked in part to intrinsic alterations of skeletal muscle with decreases in both the production of ATP by mitochondria and the transfer of energy through the phosphotransfer kinases.

Role of SIRT2 in regulating the dexamethasone-activated autophagy pathway in skeletal muscle atrophy

2021 ◽  
Author(s):  
Ziqiu HAN ◽  
Cen CHANG ◽  
Weiyi ZHU ◽  
Yanlei ZHANG ◽  
Jing ZHENG ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Skeletal Muscles ◽  
Weight Ratio ◽  
Beclin 1 ◽  
C2c12 Cells ◽  
Skeletal Muscle Atrophy ◽  
Time To Exhaustion ◽  
Endurance Capacity ◽  
Polymerase Chain Reaction Inhibition

The proteolytic autophagy system is involved in a major regulatory pathway in dexamethasone (Dex)-induced muscle atrophy. Sirtuin 2 (SIRT2) is known to participate in modulating autophagy signaling, exerting effects in skeletal muscle atrophy. We aimed to determine the effects of SIRT2 on autophagy in Dex-induced myoatrophy. Mice were randomly divided into the normal, Dex, and sirtinol groups. C2C12 cells were differentiated into myotubes and transfected with short hairpin (sh)-Sirt2-green fluorescent protein (GFP) or Sirt2-GFP lentivirus. To evaluate the mass and function of skeletal muscles, we measured the myofiber cross-sectional area, myotube size, gastrocnemius muscle wet weight/body weight ratio (%), and time-to-exhaustion. The SIRT2, myosin heavy chain (MyHC), LC3, and Beclin-1 expression levels were detected by western blotting and quantitative reverse transcription-polymerase chain reaction. Inhibition of SIRT2 markedly attenuated the muscle mass and endurance capacity. The same phenotype was observed in Sirt2-shRNA-treated myotubes, as evidenced by their decreased size. Conversely, SIRT2 overexpression alleviated Dex-induced myoatrophy in vitro. Moreover, SIRT2 negatively regulated the expression of the LC3b and Beclin-1 in skeletal muscles. These findings suggested that SIRT2 activation protects myotubes against Dex-induced atrophy through the inhibition of the autophagy system; this phenomenon may potentially serve as a target for treating glucocorticoid-induced myopathy.

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