Abstract
The heart is a pump, but also a furnace able to produce at each moment a large amount of energy and to adapt fast enough to face the changes in both fuel supply and energy demand. The pharmacological treatment of angina has been largely focused on the “pump” through hemodynamic agents aimed at decreasing cardiac effort to decrease energy demand. A new concept arose focusing the “furnace” through metabolic agents aimed at decreasing the oxygen cost of ATP production. This goal can be achieved by shifting energy production from fatty acid β-oxidation to glucose oxidation. CPT1 inhibitors were developed to prevent the fatty acid entry into mitochondria but induced cardiac hypertrophy. Regulation of carnitine biology either by carnitine supply or by γ-butyrobetaine hydroxylase inhibitors have led to controversial data both in pharmacological and clinical concerns. Trimetazidine and ranolazine increase the glucose / fatty acid oxidation balance and exhibit benefical effects in animal studies as well as in clinical trials, both in monotherapy and in association with a traditional hemodynamic drug. The association of metabolic and hemodynamic agents brings additive benefits in angina, whereas associations of hemodynamics do not. The mecanism of these drugs has not been fully understood in terms of specific target. In animal studies, dietary docosahexaenoic acid allowed similar protection, through a mechanism related to membrane conformation without specific enzymic target. From the mechanistic research published in this field, enough has now been understood to foresee some future possible targets, mainly related to the cardiomyocyte fatty acid metabolism.
Keywords: atp, cardiac myocyte, pyruvate dehydrogenase, ischaemia, phosphorylation, respiratory chain, mitochondria, Carnitine Palmitoy
Current Pharmaceutical Design
Title: Effectors of Fatty Acid Oxidation Reduction: Promising New Anti-Ischaemic Agents
Volume: 11 Issue: 4
Author(s): Alain Grynberg
Affiliation:
Keywords: atp, cardiac myocyte, pyruvate dehydrogenase, ischaemia, phosphorylation, respiratory chain, mitochondria, Carnitine Palmitoy
Abstract: The heart is a pump, but also a furnace able to produce at each moment a large amount of energy and to adapt fast enough to face the changes in both fuel supply and energy demand. The pharmacological treatment of angina has been largely focused on the “pump” through hemodynamic agents aimed at decreasing cardiac effort to decrease energy demand. A new concept arose focusing the “furnace” through metabolic agents aimed at decreasing the oxygen cost of ATP production. This goal can be achieved by shifting energy production from fatty acid β-oxidation to glucose oxidation. CPT1 inhibitors were developed to prevent the fatty acid entry into mitochondria but induced cardiac hypertrophy. Regulation of carnitine biology either by carnitine supply or by γ-butyrobetaine hydroxylase inhibitors have led to controversial data both in pharmacological and clinical concerns. Trimetazidine and ranolazine increase the glucose / fatty acid oxidation balance and exhibit benefical effects in animal studies as well as in clinical trials, both in monotherapy and in association with a traditional hemodynamic drug. The association of metabolic and hemodynamic agents brings additive benefits in angina, whereas associations of hemodynamics do not. The mecanism of these drugs has not been fully understood in terms of specific target. In animal studies, dietary docosahexaenoic acid allowed similar protection, through a mechanism related to membrane conformation without specific enzymic target. From the mechanistic research published in this field, enough has now been understood to foresee some future possible targets, mainly related to the cardiomyocyte fatty acid metabolism.
Export Options
About this article
Cite this article as:
Grynberg Alain, Effectors of Fatty Acid Oxidation Reduction: Promising New Anti-Ischaemic Agents, Current Pharmaceutical Design 2005; 11 (4) . https://dx.doi.org/10.2174/1381612053382061
DOI https://dx.doi.org/10.2174/1381612053382061 |
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
-
Oxidative Stress and Cardiovascular Aging: Interaction Between NRF-2 and ADMA
Current Cardiology Reviews Linalool as a Therapeutic and Medicinal Tool in Depression Treatment: A Review
Current Neuropharmacology Genetic Predisposition in NAFLD and NASH: Impact on Severity of Liver Disease and Response to Treatment
Current Pharmaceutical Design Targeted Cancer Therapy; Nanotechnology Approaches for Overcoming Drug Resistance
Current Medicinal Chemistry Pharmacological manipulation of peripheral vascular resistance in special clinical situations after pediatric cardiac surgery
Current Vascular Pharmacology Drug Repositioning: A Smart Approach for Combating SARS-CoV-2
Anti-Infective Agents The Hepatic Lipidome: A Gateway to Understanding the Pathogenes is of Alcohol-Induced Fatty Liver
Current Molecular Pharmacology Cardiovascular disease management through restrained inflammatory responses
Current Pharmaceutical Design Estrogen Receptor-Positive and Estrogen Receptor-Negative Human Breast Cancer Cells: Regulation of Expression of Cancer-Related Genes by Estradiol and Tamoxifen
Current Signal Transduction Therapy Use of Peripheral Blood Stem Cells in Tissue Engineering
Current Tissue Engineering (Discontinued) Biomarkers Associated with Atrial Fibrosis and Remodeling
Current Medicinal Chemistry TiO2-Nanowired Delivery of Mesenchymal Stem Cells Thwarts Diabetes- Induced Exacerbation of Brain Pathology in Heat Stroke: An Experimental Study in the Rat Using Morphological and Biochemical Approaches
CNS & Neurological Disorders - Drug Targets Dendritic Cell Homeostasis in the Regulation of Self-Reactivity
Current Pharmaceutical Design Role of Chymase in Preeclampsia
Current Vascular Pharmacology Nanomedicine for Gene Delivery for the Treatment of Cardiovascular Diseases
Current Gene Therapy Tissue Engineering and Regenerative Medicine Potentialities of Materials - Based Novel Constructs - A Review
Current Regenerative Medicine (Discontinued) Sudden Infant Death Syndrome from Epidemiology to Pathophysiology
Current Pediatric Reviews Co-Enzyme Q10 to Treat Neurological Disorders: Basic Mechanisms, Clinical Outcomes, and Future Research Direction
CNS & Neurological Disorders - Drug Targets Indications for Heart Transplantation in Congenital Heart Disease
Current Cardiology Reviews The Clinical Problems of Hypertension Treatment in Hemodialysis Patients
Current Vascular Pharmacology