Abstract
Heart failure, the common end-point of many cardiac diseases, is a major contributor to mortality and morbidity and contributes considerably to health care costs. Current treatment regimens include β-adrenergic antagonists, angiotensin converting enzyme inhibitors, and inotropic agents are used by some patients. Studies in experimental animals have demonstrated that inhibition of signaling pathways downstream of the heterotrimeric G protein Gq reduces ventricular hypertrophy and protects from the development of heart failure. However, targets identified, to date, have been limited by a lack of tissue specificity. In cardiomyocytes, Gq activates only one splice variant of one subtype of phospholipase Cβ, specifically phospholipase Cβ1b (PLCβ1b) and PLCβ1b is responsible for Gq mediated hypertrophic and apoptotic responses. PLCβ1b targets the sarcolemma via its unique C-terminal sequence and its activation can be inhibited by expressing the C-terminal sequence to compete for sarcolemmal binding. Inhibition of PLCβ1b by the C-terminal peptide reduces hypertrophic responses in cardiomyocytes. We present the evidence that inhibition of the sarcolemmal association of PLCβ1b provides a cardiac-specific target for the development of drugs to reduce pathological cardiac hypertrophy and thereby to reduce the burden of heart failure.
Keywords: Cardiomyocyte, hypertrophy, apoptosis, mini-gene inhibitor, C-terminal peptide, proline-rich domains, phospholipase C, Gq
Current Drug Targets
Title: Potential Treatment of Cardiac Hypertrophy and Heart Failure by Inhibiting the Sarcolemmal Binding of Phospholipase Cβ1b
Volume: 11 Issue: 8
Author(s): E.A. Woodcock, D.R. Grubb and P. Iliades
Affiliation:
Keywords: Cardiomyocyte, hypertrophy, apoptosis, mini-gene inhibitor, C-terminal peptide, proline-rich domains, phospholipase C, Gq
Abstract: Heart failure, the common end-point of many cardiac diseases, is a major contributor to mortality and morbidity and contributes considerably to health care costs. Current treatment regimens include β-adrenergic antagonists, angiotensin converting enzyme inhibitors, and inotropic agents are used by some patients. Studies in experimental animals have demonstrated that inhibition of signaling pathways downstream of the heterotrimeric G protein Gq reduces ventricular hypertrophy and protects from the development of heart failure. However, targets identified, to date, have been limited by a lack of tissue specificity. In cardiomyocytes, Gq activates only one splice variant of one subtype of phospholipase Cβ, specifically phospholipase Cβ1b (PLCβ1b) and PLCβ1b is responsible for Gq mediated hypertrophic and apoptotic responses. PLCβ1b targets the sarcolemma via its unique C-terminal sequence and its activation can be inhibited by expressing the C-terminal sequence to compete for sarcolemmal binding. Inhibition of PLCβ1b by the C-terminal peptide reduces hypertrophic responses in cardiomyocytes. We present the evidence that inhibition of the sarcolemmal association of PLCβ1b provides a cardiac-specific target for the development of drugs to reduce pathological cardiac hypertrophy and thereby to reduce the burden of heart failure.
Export Options
About this article
Cite this article as:
Woodcock E.A., Grubb D.R. and Iliades P., Potential Treatment of Cardiac Hypertrophy and Heart Failure by Inhibiting the Sarcolemmal Binding of Phospholipase Cβ1b, Current Drug Targets 2010; 11 (8) . https://dx.doi.org/10.2174/138945010791591331
DOI https://dx.doi.org/10.2174/138945010791591331 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...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
Related Articles
-
Tissue Engineering for Post-Myocardial Infarction Ventricular Remodeling
Mini-Reviews in Medicinal Chemistry Acute Coronary Syndromes: A Role of Immune System
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Myocardial Cellular Damage and Antioxidant Status in Off-Pump Versus On-Pump Coronary Artery Bypass Grafting - A Prospective Study
Vascular Disease Prevention (Discontinued) The Mediterranean and other Dietary Patterns in Secondary Cardiovascular Disease Prevention: A Review
Current Vascular Pharmacology Aspirin Intolerance: Experimental Models for Bed-to-Bench
Current Drug Targets Stem Cell Differentiation Stage Factors from Zebrafish Embryo: A Novel Strategy to Modulate the Fate of Normal and Pathological Human (Stem) Cells
Current Pharmaceutical Biotechnology Left Ventricular Noncompaction: New Insights into a Poorly Understood Disease
Current Cardiology Reviews Lung Ultrasound in the Critically Ill Neonate
Current Pediatric Reviews Clinical Applications of Positron Emission Tomography (PET) Imaging in Medicine: Oncology, Brain Diseases and Cardiology
Current Radiopharmaceuticals The Tree of Sirtuins and the Garden of Cardiovascular Youth
Current Vascular Pharmacology Algorithms and Criteria for Transcatheter Aortic Valve Replacement Patient Selection: Current Status and Future Trends
Current Pharmaceutical Design Stem Cell Regenerative Potential Combined with Nanotechnology and Tissue Engineering for Myocardial Regeneration
Current Stem Cell Research & Therapy Adiponectin and Cardiovascular Disease: Mechanisms and New Therapeutic Approaches
Current Medicinal Chemistry New Oral Anticoagulation after Heart Valve Replacement
Cardiovascular & Hematological Disorders-Drug Targets L-Arginine in the Prevention and Treatment of Cardiovascular Disease: From Basic to Clinical Research Studies
Vascular Disease Prevention (Discontinued) Viral Anti-Inflammatory Reagents: The Potential for Treatment of Arthritic and Vasculitic Disorders
Endocrine, Metabolic & Immune Disorders - Drug Targets Inhibitory Role of Resveratrol in the Development of Profibrogenesis and Fibrosis Mechanisms
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Cardiac Involvement in ANCA (+) and ANCA (-) Churg-Strauss Syndrome Evaluated by Cardiovascular Magnetic Resonance
Inflammation & Allergy - Drug Targets (Discontinued) Novel Anticancer Targets and Drug Discovery in Post Genomic Age
Current Medicinal Chemistry - Anti-Cancer Agents Comprehensive Analysis of SARS-COV-2 Drug Targets and Pharmacological Aspects in Treating the COVID-19
Current Molecular Pharmacology