Abstract
In the last twenty years, numerous reports provided solid evidence on the involvement of the mitochondrial permeability transition pore (PTP) in myocardial injury caused by ischemia and reperfusion. Indeed, significant cardioprotection is obtained by reducing the open probability of the PTP. This goal has been achieved by pharmacological and genetic interventions aimed at inhibiting cyclophilin D (CyPD), a regulatory protein that favors PTP opening. On the other hand, CyPD inhibition or deletion has been shown to worsen remodeling of the hypertrophic heart, an adverse outcome that must find an explanation within PTP modulation by CyPD. In this review, recent advancements in defining the molecular identity of the PTP are analyzed in relation to its pathophysiological functions and pharmacological modulation. In this respect, advantages and limitations of compounds targeting CyPD are discussed with the analysis of novel PTP inhibitors that do not interact with CyPD.
Keywords: Permeability transition, cyclophilin D, reactive oxygen species, calcium, ischemia, heart.
Current Medicinal Chemistry
Title:Modulation of Mitochondrial Permeability Transition in Ischemia-Reperfusion Injury of the Heart. Advantages and Limitations
Volume: 22 Issue: 20
Author(s): Fabio Di Lisa and Paolo Bernardi
Affiliation:
Keywords: Permeability transition, cyclophilin D, reactive oxygen species, calcium, ischemia, heart.
Abstract: In the last twenty years, numerous reports provided solid evidence on the involvement of the mitochondrial permeability transition pore (PTP) in myocardial injury caused by ischemia and reperfusion. Indeed, significant cardioprotection is obtained by reducing the open probability of the PTP. This goal has been achieved by pharmacological and genetic interventions aimed at inhibiting cyclophilin D (CyPD), a regulatory protein that favors PTP opening. On the other hand, CyPD inhibition or deletion has been shown to worsen remodeling of the hypertrophic heart, an adverse outcome that must find an explanation within PTP modulation by CyPD. In this review, recent advancements in defining the molecular identity of the PTP are analyzed in relation to its pathophysiological functions and pharmacological modulation. In this respect, advantages and limitations of compounds targeting CyPD are discussed with the analysis of novel PTP inhibitors that do not interact with CyPD.
Export Options
About this article
Cite this article as:
Lisa Di Fabio and Bernardi Paolo, Modulation of Mitochondrial Permeability Transition in Ischemia-Reperfusion Injury of the Heart. Advantages and Limitations, Current Medicinal Chemistry 2015; 22 (20) . https://dx.doi.org/10.2174/0929867322666150530210005
DOI https://dx.doi.org/10.2174/0929867322666150530210005 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Benefits of L-Arginine on Cardiovascular System
Mini-Reviews in Medicinal Chemistry The Importance of Novel Inflammatory Biomarkers in Renal Disease
Current Medicinal Chemistry Vehicles for Lipophilic Drugs: Implications for Experimental Design, Neuroprotection, and Drug Discovery
Current Neurovascular Research Relevance of Sphingolipids in the Pleiotropic Protective Effects of High-Density Lipoproteins
Current Pharmaceutical Design Strategic Leukofiltration in Cardiac Surgery
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Inflammasome as a New Therapeutic Target for Diabetic Complications
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery β-Adrenergic Over-Stimulation and Cardio-Myocyte Apoptosis: Two Receptors, One Organelle, Two Fates?
Current Drug Targets Heme Oxygenase-1 and Breast Cancer Resistance Protein Protect Against Hemeinduced Toxicity
Current Pharmaceutical Design The Cellular Effects of Carbon Monoxide in the Airway
Current Molecular Medicine Matrix Metalloproteinases as Potential Targets in the Venous Dilation Associated with Varicose Veins
Current Drug Targets How to Keep Oxidative Stress Under Control?
Current Nutrition & Food Science Effects of Tea Catechins on Inflammation-Related Cardiovascular Diseases
Current Immunology Reviews (Discontinued) Endothelin and the Ischaemic Heart
Current Vascular Pharmacology Novel Imaging Techniques in Acute Kidney Injury
Current Drug Targets Subcutaneous Immunoglobulins: A Promising Alternative for Immunomodulation?
Current Pharmaceutical Design Mechanisms of Tumor Cell Necrosis
Current Pharmaceutical Design Adenosine and ATP Receptors in the Brain
Current Topics in Medicinal Chemistry Albumin Induces Neuroprotection Against Ischemic Stroke by Altering Toll-Like Receptor 4 and Regulatory T Cells in Mice
CNS & Neurological Disorders - Drug Targets Manual Thrombectomy During Primary Coronary Intervention in Acute Myocardial Infarction: A Brief Review
Reviews on Recent Clinical Trials Biochemical Strategies to Anticoagulation: A Comparative Overview
Current Vascular Pharmacology