Abstract
The NRG/erbB pathway has emerged as an important therapeutic target for cancer growth as well as cardiac related diseases. This discovery stems back to findings showing that overexpression of erbB2 receptors increases the metastatic potential of breast cancer in patients. Blocking this receptor using a monoclonal antibody (trastuzumab) inhibits tumor growth and offers significantly improved outcomes. However, excitement over this discovery was tempered by data showing that trastuzumab-treated patients have an increased risk of developing cardiac dysfunction, limiting the clinical potential of this novel agent. This finding suggested an important protective effect of the erbB signaling pathway on cardiac survival and homeostasis. Further investigation has shown that endothelial-derived neuregulin (a key ligand for erbB receptors) has a protective paracrine effect on cardiac cells as well as vascular smooth muscle cells in the setting of an injury. Since endothelial cells contain erbB receptors, they are also targets for autocrine signaling via this pathway, an important mediator of vascular preservation and angiogenic responses of endothelium. In this review we summarize important clinical findings as well as animal and cellular models that illustrate the signaling pathways involved in vascular cell regulation of cardiomyocyte survival and angiogenesis via the NRG/erbB pathway.
Keywords: erbB, neuregulin, endothelial cells, trastuzumab, cancer, heart failure, smooth muscle cells, angiogenesis.
Current Pharmaceutical Design
Title:Cardiovascular Effects of Neuregulin-1/ErbB Signaling: Role in Vascular Signaling and Angiogenesis
Volume: 20 Issue: 30
Author(s): Nadia Hedhli, April Kalinowski and Kerry S. Russell
Affiliation:
Keywords: erbB, neuregulin, endothelial cells, trastuzumab, cancer, heart failure, smooth muscle cells, angiogenesis.
Abstract: The NRG/erbB pathway has emerged as an important therapeutic target for cancer growth as well as cardiac related diseases. This discovery stems back to findings showing that overexpression of erbB2 receptors increases the metastatic potential of breast cancer in patients. Blocking this receptor using a monoclonal antibody (trastuzumab) inhibits tumor growth and offers significantly improved outcomes. However, excitement over this discovery was tempered by data showing that trastuzumab-treated patients have an increased risk of developing cardiac dysfunction, limiting the clinical potential of this novel agent. This finding suggested an important protective effect of the erbB signaling pathway on cardiac survival and homeostasis. Further investigation has shown that endothelial-derived neuregulin (a key ligand for erbB receptors) has a protective paracrine effect on cardiac cells as well as vascular smooth muscle cells in the setting of an injury. Since endothelial cells contain erbB receptors, they are also targets for autocrine signaling via this pathway, an important mediator of vascular preservation and angiogenic responses of endothelium. In this review we summarize important clinical findings as well as animal and cellular models that illustrate the signaling pathways involved in vascular cell regulation of cardiomyocyte survival and angiogenesis via the NRG/erbB pathway.
Export Options
About this article
Cite this article as:
Hedhli Nadia, Kalinowski April and Russell S. Kerry, Cardiovascular Effects of Neuregulin-1/ErbB Signaling: Role in Vascular Signaling and Angiogenesis, Current Pharmaceutical Design 2014; 20 (30) . https://dx.doi.org/10.2174/1381612819666131125151058
DOI https://dx.doi.org/10.2174/1381612819666131125151058 |
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
-
New Applications of Oleanolic Acid and its Derivatives as Cardioprotective Agents: A Review of their Therapeutic Perspectives
Current Pharmaceutical Design Genetics and Heart Failure: A Concise Guide for the Clinician
Current Cardiology Reviews Combinations Against Combinations: Associations of Anti-HIV 1 Reverse Transcriptase Drugs Challenged by Constellations of Drug Resistance Mutations
Current Drug Metabolism Chemistry and Pharmacology of Bioactive Molecule -Coenzyme Q10: A Brief Note
Current Bioactive Compounds Natural Alkaloids and Diabetes Mellitus: A Review
Endocrine, Metabolic & Immune Disorders - Drug Targets Autophagy as a Molecular Target of Flavonoids Underlying their Protective Effects in Human Disease
Current Medicinal Chemistry Endoplasmic Reticulum Stress in Arterial Smooth Muscle Cells: A Novel Regulator of Vascular Disease
Current Cardiology Reviews The Emerging Role of Vascular Endothelial Growth Factor (VEGF) in Vascular Homeostasis: Lessons from Recent Trials with Anti-VEGF Drugs
Current Vascular Pharmacology Sympathetic Activation in Congestive Heart Failure: Evidence, Consequences and Therapeutic Implications
Current Vascular Pharmacology Endothelial Microparticles: Mediators or Markers of Endothelial Cell Dysfunction?
Current Hypertension Reviews Genetic Predisposition in NAFLD and NASH: Impact on Severity of Liver Disease and Response to Treatment
Current Pharmaceutical Design Catheter Ablation of Lone Atrial Fibrillation
Current Pharmaceutical Design Strain and Strain Rate Imaging by Echocardiography - Basic Concepts and Clinical Applicability
Current Cardiology Reviews Subject Index to Volume 2
Current Vascular Pharmacology Patent Annotations
Recent Patents on Cardiovascular Drug Discovery Engineered Nanoparticles Against MDR in Cancer: The State of the Art and its Prospective
Current Pharmaceutical Design Role of Pancreatic β-Cell Death and Cell Death-Associated Inflammation in Diabetes
Current Molecular Medicine The Vectorcardiogram and the Main Dromotropic Disturbances
Current Cardiology Reviews The Use of Exercise Echocardiography in the Evaluation of Mitral Regurgitation
Current Cardiology Reviews Monoclonal Antibody-Based Targeted Therapy in Breast Cancer
Current Medicinal Chemistry - Anti-Cancer Agents