Abstract
The purpose of this review is to enlighten the mechanisms of skeletal muscle dysfunction in heart failure. The muscle hypothesis suggests that chronic heart failure (CHF) symptoms, dyspnoea and fatigue are due to skeletal muscle alterations. Hyperventilation due to altered ergoreflex seems to be the cause of shortness of breath. Qualitative and quantitative changes occurring in the skeletal muscle, such as muscle wastage and shift from slow to fast fibers type, are likely to be responsible for fatigue. Mechanisms leading to muscle wastage in chronic heart failure, include cytokine-triggered skeletal muscle apoptosis, but also ubiquitin/proteasome and non-ubiquitin-dependent pathways. The regulation of fibre type involves the growth hormone/insulin-like growth factor 1/calcineurin/ transcriptional coactivator PGC1 cascade. The imbalance between protein synthesis and degradation plays an important role. Protein degradation can occur through ubiquitin-dependent and non-ubiquit-independent pathways. Systems controlling ubiquitin/ proteasome activation have been described. These are triggered by tumour necrosis factor and growth hormone/ insulin-like growth factor 1. However, an important role is played by apoptosis. In humans, and experimental models of heart failure, programmed cell death has been found in skeletal muscle and interstitial cells. Apoptosis is triggered by tumour necrosis factor and in vitro experiments have shown that it can be induced by its second messenger sphingosine. Apoptosis correlates with the severity of the heart failure syndrome. It involves activation of caspases 3 and 9 and mitochondrial cytochrome c release. Sarcomeric protein oxidation and its consequent contractile impairment can form another cause of skeletal muscle dysfunction in CHF.
Keywords: Heart failure, skeletal muscle, apoptosis, oxidative stress, atrophy, cytokines
Current Pharmaceutical Design
Title: Physiological Basis for Contractile Dysfunction in Heart Failure
Volume: 14 Issue: 25
Author(s): Luciano Dalla Libera, Giorgio Vescovo and Maurizio Volterrani
Affiliation:
Keywords: Heart failure, skeletal muscle, apoptosis, oxidative stress, atrophy, cytokines
Abstract: The purpose of this review is to enlighten the mechanisms of skeletal muscle dysfunction in heart failure. The muscle hypothesis suggests that chronic heart failure (CHF) symptoms, dyspnoea and fatigue are due to skeletal muscle alterations. Hyperventilation due to altered ergoreflex seems to be the cause of shortness of breath. Qualitative and quantitative changes occurring in the skeletal muscle, such as muscle wastage and shift from slow to fast fibers type, are likely to be responsible for fatigue. Mechanisms leading to muscle wastage in chronic heart failure, include cytokine-triggered skeletal muscle apoptosis, but also ubiquitin/proteasome and non-ubiquitin-dependent pathways. The regulation of fibre type involves the growth hormone/insulin-like growth factor 1/calcineurin/ transcriptional coactivator PGC1 cascade. The imbalance between protein synthesis and degradation plays an important role. Protein degradation can occur through ubiquitin-dependent and non-ubiquit-independent pathways. Systems controlling ubiquitin/ proteasome activation have been described. These are triggered by tumour necrosis factor and growth hormone/ insulin-like growth factor 1. However, an important role is played by apoptosis. In humans, and experimental models of heart failure, programmed cell death has been found in skeletal muscle and interstitial cells. Apoptosis is triggered by tumour necrosis factor and in vitro experiments have shown that it can be induced by its second messenger sphingosine. Apoptosis correlates with the severity of the heart failure syndrome. It involves activation of caspases 3 and 9 and mitochondrial cytochrome c release. Sarcomeric protein oxidation and its consequent contractile impairment can form another cause of skeletal muscle dysfunction in CHF.
Export Options
About this article
Cite this article as:
Libera Dalla Luciano, Vescovo Giorgio and Volterrani Maurizio, Physiological Basis for Contractile Dysfunction in Heart Failure, Current Pharmaceutical Design 2008; 14 (25) . https://dx.doi.org/10.2174/138161208786071254
DOI https://dx.doi.org/10.2174/138161208786071254 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Flavonoids as Multi-Target Compounds in Drug Discovery
Mini-Reviews in Organic Chemistry Beta-Blockers as First Line Treatment of Hypertension: A Proponents View
Current Hypertension Reviews Genetic Basis, Nutritional Challenges and Adaptive Responses in the Prenatal Origin of Obesity and Type-2 Diabetes
Current Diabetes Reviews Use and Safety of Calcium Channel Blockers in Obstetrics
Current Medicinal Chemistry Conventional and Non-Conventional Targets of Natural Products in the Management of Diabetes Mellitus and Associated Complications
Current Medicinal Chemistry Global Cardiovascular Risk Management in Primary Prevention
Current Vascular Pharmacology Present Insights on Cardiomyopathy in Diabetic Patients
Current Diabetes Reviews Herbal Medicine of the 21st Century: A Focus on the Chemistry, Pharmacokinetics and Toxicity of Five Widely Advocated Phytotherapies
Current Topics in Medicinal Chemistry Interval Exercise Therapy for Type 2 Diabetes
Current Diabetes Reviews TGF-beta Signaling in Cancer Treatment
Current Pharmaceutical Design A Focus on Pharmacological Management of Catecholaminergic Polymorphic Ventricular Tachycardia
Mini-Reviews in Medicinal Chemistry Phosphatidylinositol 3-kinase Signaling as a Therapeutic Target for Cervical Cancer
Current Cancer Drug Targets Sodium-Proton Exchanger Isoform-1: Synthesis of a Potent Inhibitor Labeled with Deuterium and Carbon-14
Current Radiopharmaceuticals Prevalence of Dilated Cardiomyopathy in HIV-Infected African Patients Not Receiving HAART: A Multicenter, Observational, Prospective, Cohort Study in Rwanda
Current HIV Research In Utero Gene Therapy: Prospect and Future
Current Pharmaceutical Design Chaperone Therapy: New Molecular Therapy for Protein Misfolding Diseases with Brain Dysfunction
Current Bioinformatics Gene Therapy Approaches for Cardiovascular Diseases
Current Gene Therapy Cardiotonic Steroids in Adaptation to Dietary Salt Intake
Current Clinical Pharmacology Defining and Regulating Acute Inflammatory Lesion Formation during the Pathogenesis of Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis
CNS & Neurological Disorders - Drug Targets Involvement of Hypoxia-Inducible Factors in the Dysregulation of Oxygen Homeostasis in Sepsis
Cardiovascular & Hematological Disorders-Drug Targets