Abstract
Inflammation and genetics play an important role in the pathogenesis of coronary heart disease (CHD). However, despite the increasing appreciation of the role of genetics in CHD and myocardial infarction (MI) pathogenesis, pharmacogenomic approaches to uncover drug target have not been extensively explored. Cyclo-oxygenases (COXs) and 5-lipoxygenase (5-LO) are the key enzymes in the conversion of arachidonic acid to prostaglandins (PG) and leukotrienes (LT) and are implicated in a wide variety of inflammatory disorders, including atherosclerosis. In fact, PGE2 activates Matrix Metallo-proteinases whereas LTB4 is a chemoactractant for monocytes and activates gene expression in inflammatory cells. We have tested the hypothesis that anti-inflammatory variants of these genes confer genetic resistance to MI and conversely favour longevity. So, we analyzed MI patients, age-related controls and centenarians. The proinflammatory alleles of COX-2 and 5-LO were overrepresented in MI and under-represented in centenarians whereas agerelated controls displayed intermediate values. MI is a multifactorial disease, hence MI might be the result of a cumulative effect which contributes with different timing to achieve a threshold where the chance to develop the diseases is very high. In particular, differences in inflammatory status can contribute to the chance of developing a risk phenotype. However, these studies might contribute to the determination of a risk profile which may allow both the early identification of individuals susceptible to disease and the possible discovery of potential targets for drug.
Keywords: Immunogenetics, Infarction, Inflammation, Longevity, Pharmacogenomics
Current Pharmaceutical Design
Title: Pro-Inflammatory Gene Variants in Myocardial Infarction and Longevity: Implications for Pharmacogenomics
Volume: 14 Issue: 26
Author(s): F. Listi, M. Caruso, E. Incalcaterra, E. Hoffmann, G. Caimi, C. R. Balistreri, S. Vasto, V. Scafidi, C. Caruso and G. Candore
Affiliation:
Keywords: Immunogenetics, Infarction, Inflammation, Longevity, Pharmacogenomics
Abstract: Inflammation and genetics play an important role in the pathogenesis of coronary heart disease (CHD). However, despite the increasing appreciation of the role of genetics in CHD and myocardial infarction (MI) pathogenesis, pharmacogenomic approaches to uncover drug target have not been extensively explored. Cyclo-oxygenases (COXs) and 5-lipoxygenase (5-LO) are the key enzymes in the conversion of arachidonic acid to prostaglandins (PG) and leukotrienes (LT) and are implicated in a wide variety of inflammatory disorders, including atherosclerosis. In fact, PGE2 activates Matrix Metallo-proteinases whereas LTB4 is a chemoactractant for monocytes and activates gene expression in inflammatory cells. We have tested the hypothesis that anti-inflammatory variants of these genes confer genetic resistance to MI and conversely favour longevity. So, we analyzed MI patients, age-related controls and centenarians. The proinflammatory alleles of COX-2 and 5-LO were overrepresented in MI and under-represented in centenarians whereas agerelated controls displayed intermediate values. MI is a multifactorial disease, hence MI might be the result of a cumulative effect which contributes with different timing to achieve a threshold where the chance to develop the diseases is very high. In particular, differences in inflammatory status can contribute to the chance of developing a risk phenotype. However, these studies might contribute to the determination of a risk profile which may allow both the early identification of individuals susceptible to disease and the possible discovery of potential targets for drug.
Export Options
About this article
Cite this article as:
Listi F., Caruso M., Incalcaterra E., Hoffmann E., Caimi G., Balistreri R. C., Vasto S., Scafidi V., Caruso C. and Candore G., Pro-Inflammatory Gene Variants in Myocardial Infarction and Longevity: Implications for Pharmacogenomics, Current Pharmaceutical Design 2008; 14 (26) . https://dx.doi.org/10.2174/138161208786264115
DOI https://dx.doi.org/10.2174/138161208786264115 |
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
-
Dendritic Cells in Pathogenesis of COPD
Current Pharmaceutical Design Systemic Fungal Infections Caused by Candida Species: Epidemiology, Infection Process and Virulence Attributes
Current Drug Targets Molecular Mechanisms Involved in the Aging of the T-cell Immune Response
Current Genomics Meet our Editorial Board Member
Cardiovascular & Hematological Agents in Medicinal Chemistry Ivabradine: The Hope for a Good Treatment of Ischemic Heart Disease
Current Medicinal Chemistry Periodontitis, Endothelial Dysfunction and Atherosclerosis
Vascular Disease Prevention (Discontinued) Clinical Evaluation of Natural History of Peyronie’s Disease: Our Experience, Old Myths and New Certainties
Inflammation & Allergy - Drug Targets (Discontinued) Developments of Anticoagulants and New Agents with Anti-Coagulant Effects in Deep Vein Thrombosis
Mini-Reviews in Medicinal Chemistry C. elegans Genetic Networks Predict Roles for O-GlcNAc Cycling in Key Signaling Pathways
Current Signal Transduction Therapy Strain Imaging Echocardiography: What Imaging Cardiologists Should Know
Current Cardiology Reviews Arterial Stiffness, Cognitive Dysfunction and Adherence to Antihypertensive Agents. Is there a Link to Hypertensive Patients?
Current Vascular Pharmacology Acute Coronary Syndromes in Patients with Atrial Fibrillation and Heart Failure. Could Novel Oral Anticoagulants be the Solution of the Optimal Antithrombotic Therapy Puzzle?
Cardiovascular & Hematological Agents in Medicinal Chemistry Reactive Oxygen Species in Vascular Wall
Cardiovascular & Hematological Disorders-Drug Targets Chemoprevention of Colorectal Cancer: Ready for Routine Use?
Current Topics in Medicinal Chemistry Adipose Tissue: The Link Between Obesity and Cardiovascular Disease
Cardiovascular & Hematological Disorders-Drug Targets Platelet and Soluble Glycoprotein VI - Novel Applications in Diagnosis and Therapy
Current Drug Targets Recent Advances and Patents on Novel Devices for Minimally Invasive Treatment of Functional Mitral Regurgitation
Recent Patents on Biomedical Engineering (Discontinued) New Targets for Anticoagulation and Future Perspectives
Current Drug Discovery Technologies Evidence-Based Percutaneous Closure of the Left Atrial Appendage in Patients with Atrial Fibrillation
Current Cardiology Reviews Gut Microbiota, Obesity and Bariatric Surgery: Current Knowledge and Future Perspectives
Current Pharmaceutical Design