Abstract
Pulmonary arterial hypertension (PAH) is a disease characterized by a progressive increase in pulmonary arterial pressure leading to right ventricular hypertrophy, right heart failure and ultimately to death. PAH is a disease of small pulmonary arteries inducing vascular narrowing leading to a progressive increase in pulmonary vascular resistance. The therapeutic means that improve PAH are still very limited and are too often restricted to heart/lungs transplantation. Numerous forms of pulmonary hypertension exist. Although it is still unclear as to all types of PAH share a common pathogenesis, it is generally admitted that pulmonary vasoconstriction and remodelling of the arterial wall are key events. In this review, we discuss pulmonary artery smooth muscle cells (PASMC) ion channels implication in both phenomena and we examine whether variations in expression and/or the activity of these channels can contribute to the development of PAH with special attention to K+, Cl- and voltage- and non voltage-activated Ca2+ channels. For each family of ion channels, we describe their implication in the control of both membrane potential and resting cytosolic calcium concentration which are key parameters of PASMC in PAH. We also provide evidence for an implication of these channels in not only vasoconstriction but also proliferation and/or decreased apoptosis of PASMC, phenomena which contribute to remodelling of pulmonary arterial wall. In this respect, PAH may be considered as form of vascular “channelopathy”. Finally, we present examples of some substances acting on ion channels and thus potentially constituting innovative therapeutic approaches of PAH.
Keywords: Pulmonary hypertension, pulmonary artery, ion channels, vascular smooth muscle, vasoconstriction, remodelling, pathophysiology, therapeutic targets
Current Pharmaceutical Design
Title: Modulation of Ion Channels in Pulmonary Arterial Hypertension
Volume: 13 Issue: 24
Author(s): Christelle Guibert, Roger Marthan and Jean-Pierre Savineau
Affiliation:
Keywords: Pulmonary hypertension, pulmonary artery, ion channels, vascular smooth muscle, vasoconstriction, remodelling, pathophysiology, therapeutic targets
Abstract: Pulmonary arterial hypertension (PAH) is a disease characterized by a progressive increase in pulmonary arterial pressure leading to right ventricular hypertrophy, right heart failure and ultimately to death. PAH is a disease of small pulmonary arteries inducing vascular narrowing leading to a progressive increase in pulmonary vascular resistance. The therapeutic means that improve PAH are still very limited and are too often restricted to heart/lungs transplantation. Numerous forms of pulmonary hypertension exist. Although it is still unclear as to all types of PAH share a common pathogenesis, it is generally admitted that pulmonary vasoconstriction and remodelling of the arterial wall are key events. In this review, we discuss pulmonary artery smooth muscle cells (PASMC) ion channels implication in both phenomena and we examine whether variations in expression and/or the activity of these channels can contribute to the development of PAH with special attention to K+, Cl- and voltage- and non voltage-activated Ca2+ channels. For each family of ion channels, we describe their implication in the control of both membrane potential and resting cytosolic calcium concentration which are key parameters of PASMC in PAH. We also provide evidence for an implication of these channels in not only vasoconstriction but also proliferation and/or decreased apoptosis of PASMC, phenomena which contribute to remodelling of pulmonary arterial wall. In this respect, PAH may be considered as form of vascular “channelopathy”. Finally, we present examples of some substances acting on ion channels and thus potentially constituting innovative therapeutic approaches of PAH.
Export Options
About this article
Cite this article as:
Christelle Guibert , Roger Marthan and Jean-Pierre Savineau , Modulation of Ion Channels in Pulmonary Arterial Hypertension, Current Pharmaceutical Design 2007; 13 (24) . https://dx.doi.org/10.2174/138161207781368585
DOI https://dx.doi.org/10.2174/138161207781368585 |
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
-
Cancer Chemoprevention by Targeting the Epigenome
Current Drug Targets Nitric Oxide and Dietary Factors: Part II Cholesterol, Fat, Amino Acids,Proteins and Carbohydrate
Vascular Disease Prevention (Discontinued) The Role of Matrix Metalloproteinases in Diabetes Mellitus
Current Topics in Medicinal Chemistry Inflammatory Related Cardiovascular Diseases: From Molecular Mechanisms to Therapeutic Targets
Current Pharmaceutical Design The Role of PPARβ/δ in the Management of Metabolic Syndrome and its Associated Cardiovascular Complications
Endocrine, Metabolic & Immune Disorders - Drug Targets Oral IIa and Xa Inhibitors for Prevention of Stroke in Atrial Fibrillation: Clinical Studies and Regulatory Considerations
Current Clinical Pharmacology GRK2 and Beta-Arrestins in Cardiovascular Disease: Established and Emerging Possibilities for Therapeutic Targeting
Current Molecular Pharmacology Statistical Methods Used for the Evaluation of Reliability and Validity of Nutrition Assessment Tools Used in Medical Research
Current Pharmaceutical Design New Approaches to the Modulation of the Cyclooxygenase-2 and 5-Lipoxygenase Pathways
Current Topics in Medicinal Chemistry Limited Hypotensive Effect of Sildenafil in a High-Risk Population: A Preliminary Report
Current Drug Safety Profiling of Multiple Signal Pathway Activities by Multiplexing Antibody and GFP-Based Translocation Assays
Combinatorial Chemistry & High Throughput Screening Remodeling of Protein Aggregates by Hsp104
Protein & Peptide Letters TRPV1 Function in Health and Disease
Current Pharmaceutical Biotechnology TRP Channels and Cancer: New Targets for Diagnosis and Chemotherapy
Endocrine, Metabolic & Immune Disorders - Drug Targets Signs and Related Mechanisms of Ethanol Hepatotoxicity
Current Drug Abuse Reviews Kidney Injury Molcule-1 in Acute and Chronic Kidney Disease
Recent Patents on Biomarkers 5-Adenosine Monophosphate-Activated Protein Kinase and the Metabolic Syndrome
Endocrine, Metabolic & Immune Disorders - Drug Targets Endovascular Repair of Thoracic Aortic Aneurysms
Recent Patents on Cardiovascular Drug Discovery Patent Selections
Recent Patents on Cardiovascular Drug Discovery Flavonoids as Sirtuin Modulators
Current Topics in Medicinal Chemistry