Abstract
Statins, inhibitors of 3-hydroxy-3-methylglutaryl-CoA are best known for their lipid-lowering effects but they also possess immunomodulatory properties that are, at least in part, independent of changes in serum cholesterol. Some recent clinical trials (eg. PROVE-IT) have shown that statins exert beneficial cardiovascular effects independently of the resultant level of LDL cholesterol. These “pleiotropic” effects seem to be due to inhibition of prenylation of several proteins such as the small GTP-binding proteins Ras and Rho, and to the disruption, or depletion, of cholesterol rich membrane micro-domains (membrane rafts). Through these pathways statins are able to modulate immune responses by modulating cytokine levels and by affecting the function of cells involved in both innate and adaptive responses. Over the past decade, a large number of studies reported a prominent role of inflammation and immune response in atherosclerosis, thus, the ability of statins to modulate immune-inflammatory processes could explain their cardiovascular beneficial effects beyond lipid-lowering effects. Moreover, various studies demonstrated beneficial effects of statins in inflammatory and auto-immune diseases, such as rheumatoid arthritis, multiple sclerosis, and others. The purpose of this review is to summarize clinical and experimental evidence of immunomodulatory properties of these drugs, highlighting their clinical and, thus, therapeutic implications.
Cardiovascular & Hematological Agents in Medicinal Chemistry
Title: Immunomodulator Activity of 3-Hydroxy-3-Methilglutaryl-CoA Inhibitors
Volume: 7 Issue: 4
Author(s): Costantino Smaldone, Salvatore Brugaletta, Vincenzo Pazzano and Giovanna Liuzzo
Affiliation:
Abstract: Statins, inhibitors of 3-hydroxy-3-methylglutaryl-CoA are best known for their lipid-lowering effects but they also possess immunomodulatory properties that are, at least in part, independent of changes in serum cholesterol. Some recent clinical trials (eg. PROVE-IT) have shown that statins exert beneficial cardiovascular effects independently of the resultant level of LDL cholesterol. These “pleiotropic” effects seem to be due to inhibition of prenylation of several proteins such as the small GTP-binding proteins Ras and Rho, and to the disruption, or depletion, of cholesterol rich membrane micro-domains (membrane rafts). Through these pathways statins are able to modulate immune responses by modulating cytokine levels and by affecting the function of cells involved in both innate and adaptive responses. Over the past decade, a large number of studies reported a prominent role of inflammation and immune response in atherosclerosis, thus, the ability of statins to modulate immune-inflammatory processes could explain their cardiovascular beneficial effects beyond lipid-lowering effects. Moreover, various studies demonstrated beneficial effects of statins in inflammatory and auto-immune diseases, such as rheumatoid arthritis, multiple sclerosis, and others. The purpose of this review is to summarize clinical and experimental evidence of immunomodulatory properties of these drugs, highlighting their clinical and, thus, therapeutic implications.
Export Options
About this article
Cite this article as:
Smaldone Costantino, Brugaletta Salvatore, Pazzano Vincenzo and Liuzzo Giovanna, Immunomodulator Activity of 3-Hydroxy-3-Methilglutaryl-CoA Inhibitors, Cardiovascular & Hematological Agents in Medicinal Chemistry 2009; 7 (4) . https://dx.doi.org/10.2174/187152509789541864
DOI https://dx.doi.org/10.2174/187152509789541864 |
Print ISSN 1871-5257 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6182 |
Call for Papers in Thematic Issues
Medicinal Plants with Beneficial Properties on Diabetes and Hypertension
Diabetes and hypertension are real scourges of the 21st century. It is imperative to act in order to find innovative solutions to this problem. Taking medications such as hypoglycemic and antihypertensive drugs may aggravate certain underlying comorbidities, such as chronic kidney disease and cardiovascular disease. This significant drawback therefore requires ...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
Related Articles
-
Anti-cytokines and Cytokines in the Treatment of Rheumatoid Arthritis
Current Pharmaceutical Design Can Tocilizumab Decrease Cartilage Oligomeric Matrix Protein Levels and Disease Activity in Patients with Long-Standing Rheumatoid Arthritis?
Current Rheumatology Reviews 6H-Indolo[2,3-b]Quinoxalines: DNA and Protein Interacting Scaffold for Pharmacological Activities
Mini-Reviews in Medicinal Chemistry New Approaches to the Modulation of the Cyclooxygenase-2 and 5-Lipoxygenase Pathways
Current Topics in Medicinal Chemistry Ankylosing Spondylitis, HLA-B27, Klebsiella and “Popper Sequences”
Current Rheumatology Reviews The Oral Administration Effect of Drug Mannuronic Acid (M2000) on Gene Expression of Matrix and Tissue Inhibitor of Metalloproteinases in Rheumatoid Arthritis Patients
Current Drug Discovery Technologies Interleukin-26, An Epitheliotropic T-Cell Cytokine
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Allosteric Inhibition of G-Protein Coupled Receptor Oligomerization: Strategies and Challenges for Drug Development
Current Topics in Medicinal Chemistry The DREAM of Pain Relief
Current Rheumatology Reviews Extrahepatic Targets and Cellular Reactivity of Drug Metabolites
Current Medicinal Chemistry The Role of Progenitor Cells in Osteoarthritis Development and Progression
Current Stem Cell Research & Therapy Pulmonary Hypertension and Lung Transplantation
Current Hypertension Reviews Recent Understanding of Leukocytapheresis (LCAP) for the Treatment of Inflammatory Bowel Disease
Current Pharmaceutical Design Systemic Lupus Erythematosus-Related Interstitial Lung Disease
Current Rheumatology Reviews Risk Factors for Myocardial Infarction in Women and Men: A Review of the Current Literature
Current Pharmaceutical Design The Effect of Interleukin 38 on Inflammation-induced Corneal Neovascularization
Current Molecular Medicine Emerging Trends in Endometriosis Treatment - Review
Current Women`s Health Reviews PDE4D Gene in the STRK1 Region on 5q12: Susceptibility Gene for Ischemic Stroke
Current Medicinal Chemistry Innovations in siRNA Research: A Technology Comes of Age
Recent Patents on Anti-Infective Drug Discovery Tachykinins and the Cardiovascular System
Current Drug Targets