Abstract
Protease-activated receptors (PARs) are a unique group of four G-protein coupled receptors. They are widely expressed within the cardiovascular system and the heart. PARs are activated via cleavage by serine proteases. In vitro and in vivo studies showed that the activation of PAR1 and PAR2 plays a crucial role in virus induced inflammatory diseases. The receptors enable cells to recognize pathogen-derived changes in the extracellular environment. An infection with Coxsackie-virus B3 (CVB3) can cause myocarditis. Recent studies have been shown that PAR1 signaling enhanced the antiviral innate immune response via interferon β (IFNβ) and thus limited the virus replication and cardiac damage. In contrast, PAR2 signaling decreased the antiviral innate immune response via IFNβ und thus increased the virus replication, which caused severe myocarditis. Along with CVB3 other viruses such as influenza A virus (IAV) and herpes simplex virus (HSV) can induce myocarditis. The role of PAR signaling in IAV infections is contrarily discussed. During HSV infections PARs facilitate the virus infection of the host cell. These studies show that PARs might be interesting drug targets for the treatment of virus infections and inflammatory heart diseases. First studies with PAR agonists, antagonists, and serine protease inhibitors have been conducted in mice. The inhibition of thrombin the main PAR1 activating protease decreased the IFNβ response and increased the virus replication in CVB3-induced myocarditis. This indicates that further studies with direct PAR agonists and antagonists are needed to determine whether PARs are useful drug targets for the therapy of virus-induced heart diseases.
Keywords: Protease-activated receptor, myocarditis, virus infection, innate immune system, tissue factor, coagulation, interferon beta, toll-like receptor.
Current Pharmaceutical Design
Title:The Role of Protease-Activated Receptors for the Development of Myocarditis: Possible Therapeutic Implications
Volume: 22 Issue: 4
Author(s): Alice Weithauser, Marco Witkowski and Ursula Rauch
Affiliation:
Keywords: Protease-activated receptor, myocarditis, virus infection, innate immune system, tissue factor, coagulation, interferon beta, toll-like receptor.
Abstract: Protease-activated receptors (PARs) are a unique group of four G-protein coupled receptors. They are widely expressed within the cardiovascular system and the heart. PARs are activated via cleavage by serine proteases. In vitro and in vivo studies showed that the activation of PAR1 and PAR2 plays a crucial role in virus induced inflammatory diseases. The receptors enable cells to recognize pathogen-derived changes in the extracellular environment. An infection with Coxsackie-virus B3 (CVB3) can cause myocarditis. Recent studies have been shown that PAR1 signaling enhanced the antiviral innate immune response via interferon β (IFNβ) and thus limited the virus replication and cardiac damage. In contrast, PAR2 signaling decreased the antiviral innate immune response via IFNβ und thus increased the virus replication, which caused severe myocarditis. Along with CVB3 other viruses such as influenza A virus (IAV) and herpes simplex virus (HSV) can induce myocarditis. The role of PAR signaling in IAV infections is contrarily discussed. During HSV infections PARs facilitate the virus infection of the host cell. These studies show that PARs might be interesting drug targets for the treatment of virus infections and inflammatory heart diseases. First studies with PAR agonists, antagonists, and serine protease inhibitors have been conducted in mice. The inhibition of thrombin the main PAR1 activating protease decreased the IFNβ response and increased the virus replication in CVB3-induced myocarditis. This indicates that further studies with direct PAR agonists and antagonists are needed to determine whether PARs are useful drug targets for the therapy of virus-induced heart diseases.
Export Options
About this article
Cite this article as:
Weithauser Alice, Witkowski Marco and Rauch Ursula, The Role of Protease-Activated Receptors for the Development of Myocarditis: Possible Therapeutic Implications, Current Pharmaceutical Design 2016; 22 (4) . https://dx.doi.org/10.2174/1381612822666151222160933
DOI https://dx.doi.org/10.2174/1381612822666151222160933 |
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
-
The Role of Inflammatory Response in Stroke Associated Programmed Cell Death
Current Neuropharmacology Cytochrome P450 Drug Metabolizing Enzymes in Roma Population Samples: Systematic Review of the Literature
Current Medicinal Chemistry Cellular Mechanisms for Diastolic Dysfunction in the Human Heart
Current Pharmaceutical Biotechnology Collateral Circulation in Chronic Total Occlusions – an interventional perspective
Current Cardiology Reviews Treatment of Leukoaraiosis: A Futuristic View
Current Drug Targets Heme Oxygenase-1 against Vascular Insufficiency: Roles of Atherosclerotic Disorders
Current Pharmaceutical Design Hypertension and Counter-Hypertension Mechanisms in Giraffes
Cardiovascular & Hematological Disorders-Drug Targets Recent Advances in Ozonation of Vegetable Oils
Recent Patents on Materials Science Metabolic Programming Nowadays (or Perhaps Now and then?)
Current Nutrition & Food Science Preface
Current Nutrition & Food Science Use of Paediatric Xylometazoline Nasal Drop is not a Child’s Play in Hypertensive Patients on Bisoprolol: A Case Report
Current Drug Safety Oral Antiplatelet Treatment in STEMI: Current Practice and Future Considerations
Current Pharmaceutical Design Cryptotanshinone Induces Pro-death Autophagy through JNK Signaling Mediated by Reactive Oxygen Species Generation in Lung Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry The Challenges in Moving from Ageing to Successful Longevity
Current Vascular Pharmacology Experimental Strategies in Autoimmunity: Antagonists of Cytokines and their Receptors, Nanocarriers, Inhibitors of Immunoproteasome, Leukocyte Migration and Protein Kinases
Current Pharmaceutical Design Management of the Low Cardiac Output Syndrome Following Surgery for Congenital Heart Disease
Current Cardiology Reviews Treating Heart Failure with Preserved Ejection Fraction Related to Arterial Stiffness. Can we Kill Two Birds With One Stone?
Current Vascular Pharmacology PPARγ Activation Improves the Molecular and Functional Components of Ito Remodeling by Angiotensin II
Current Pharmaceutical Design Enhancing Endothelial Progenitor Cell Function Through Selective Estrogen Receptor Modulation: A Potential Approach to Cardiovascular Risk Reduction
Cardiovascular & Hematological Agents in Medicinal Chemistry Patents on Technologies of Human Tissue and Organ Regeneration from Pluripotent Human Embryonic Stem Cells
Recent Patents on Regenerative Medicine