Abstract
Plasma levels of high-density lipoprotein (HDL) cholesterol and its major apolipoprotein (apo), apo A-I, are inversely correlated with the incidence of ischemic cardiovascular diseases. Till now, evaluation of the hypothesis that elevation of HDL cholesterol reduces atherosclerotic burden and/or decreases ischemic cardiovascular events in humans has been hampered by the lack of drugs that selectively increase HDL cholesterol. In contrast to the lack of clinical data, evidence for a direct causal role of HDL in modulating atherogenesis in experimental models has been provided by investigations in human apo A-I transgenic mice and rabbits. The development of gene transfer technologies with a sufficiently high therapeutic index may pave the road for a selective and effective HDL raising therapeutic intervention. The goal of a therapeutic strategy that modulates HDL metabolism is not an increase of HDL cholesterol as such, but an enhancement of HDL function. The value of HDL cholesterol as a surrogate end-point to predict reduced atherosclerosis or a decrease in clinical events may be highly dependent on the mechanism leading to an increased level of HDL cholesterol. In the case of gene transfer, this implies that beneficial effects of increasing HDL cholesterol will be dependent on the transgene that is expressed. Here, we critically review HDL metabolism and HDL function in relation to the development of HDL raising gene transfer, advances and drawbacks of different gene transfer technologies, and experimental gene transfer studies evaluating the effect of raised HDL on histological and functional outcomes in animal models.
Keywords: High-density lipoproteins, gene therapy, gene transfer, apolipoprotein A-I, atherosclerosis, reverse cholesterol transport
Current Pharmaceutical Design
Title: Gene Therapy to Improve High-Density Lipoprotein Metabolism and Function
Volume: 16 Issue: 13
Author(s): Eline Van Craeyveld, Stephanie Gordts, Frank Jacobs and Bart De Geest
Affiliation:
Keywords: High-density lipoproteins, gene therapy, gene transfer, apolipoprotein A-I, atherosclerosis, reverse cholesterol transport
Abstract: Plasma levels of high-density lipoprotein (HDL) cholesterol and its major apolipoprotein (apo), apo A-I, are inversely correlated with the incidence of ischemic cardiovascular diseases. Till now, evaluation of the hypothesis that elevation of HDL cholesterol reduces atherosclerotic burden and/or decreases ischemic cardiovascular events in humans has been hampered by the lack of drugs that selectively increase HDL cholesterol. In contrast to the lack of clinical data, evidence for a direct causal role of HDL in modulating atherogenesis in experimental models has been provided by investigations in human apo A-I transgenic mice and rabbits. The development of gene transfer technologies with a sufficiently high therapeutic index may pave the road for a selective and effective HDL raising therapeutic intervention. The goal of a therapeutic strategy that modulates HDL metabolism is not an increase of HDL cholesterol as such, but an enhancement of HDL function. The value of HDL cholesterol as a surrogate end-point to predict reduced atherosclerosis or a decrease in clinical events may be highly dependent on the mechanism leading to an increased level of HDL cholesterol. In the case of gene transfer, this implies that beneficial effects of increasing HDL cholesterol will be dependent on the transgene that is expressed. Here, we critically review HDL metabolism and HDL function in relation to the development of HDL raising gene transfer, advances and drawbacks of different gene transfer technologies, and experimental gene transfer studies evaluating the effect of raised HDL on histological and functional outcomes in animal models.
Export Options
About this article
Cite this article as:
Van Craeyveld Eline, Gordts Stephanie, Jacobs Frank and De Geest Bart, Gene Therapy to Improve High-Density Lipoprotein Metabolism and Function, Current Pharmaceutical Design 2010; 16 (13) . https://dx.doi.org/10.2174/138161210791050997
DOI https://dx.doi.org/10.2174/138161210791050997 |
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
-
Pharmacogenomics of Cardiovascular Complications in Diabetes and Obesity
Recent Patents on Biotechnology HIF Prolyl-4-hydroxylase Interacting Proteins: Consequences for Drug Targeting
Current Pharmaceutical Design Cyclosporin and Organ Specific Toxicity: Clinical Aspects, Pharmacogenetics and Perspectives
Current Clinical Pharmacology The Adipose Tissue as a Source of Vasoactive Factors
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Editorial (Thematic Issue: Therapeutic Interventions Against Trypanosomiasis)
Current Topics in Medicinal Chemistry The Role of Matrix Metalloproteinases in Diabetes Mellitus
Current Topics in Medicinal Chemistry High-Density Lipoprotein Quantity or Quality for Cardiovascular Prevention?
Current Pharmaceutical Design Cardiotoxicity of Tyrosine-Kinase-Targeting Drugs
Cardiovascular & Hematological Agents in Medicinal Chemistry Stage A: Can Heart Failure Be Prevented?
Current Cardiology Reviews Stem Cells and Cardiovascular Repair: A Role for Natural and Synthetic Molecules Harboring Differentiating and Paracrine Logics
Cardiovascular & Hematological Agents in Medicinal Chemistry Atrial Fibrillation with a Focus on Oral Antiarrhythmic Therapy
Current Drug Therapy Effects of Tea Catechins on Inflammation-Related Cardiovascular Diseases
Current Immunology Reviews (Discontinued) Kawasakis Disease, Acrodynia, and Mercury
Current Medicinal Chemistry Pharmacological and Non Pharmacological Strategies in the Management of Coronary Artery Disease and Chronic Kidney Disease
Current Cardiology Reviews Editorial (Thematic Issue: Managing Strategies for Diverse Diseases: Challenges from Bench to Bedside Translation in Successful Drug Discovery and Dev elopment (Part C))
Current Pharmaceutical Design Cardiovascular Magnetic Resonance T2-weighted Imaging of Myocardial Edema in Acute Myocardial Infarction
Recent Patents on Cardiovascular Drug Discovery Non Invasive Imaging of Myocardial Infarction with Computed Tomography and Magnetic Resonance
Current Vascular Pharmacology L-Carnitine - Metabolic Functions and Meaning in Humans Life
Current Drug Metabolism Alcohol Drinking, Apolipoprotein Polymorphisms and the Risk of Cardiovascular Diseases
Current Neurovascular Research Morphological and Molecular Changes of the Myocardium After Left Ventricular Mechanical Support
Current Cardiology Reviews