Abstract
Angiogenesis plays an important role in the pathogenesis of inflammatory diseases, including rheumatoid arthritis (RA). The site and extent of inflammation and subsequent joint destruction in the rheumatoid synovium is dependent on the development of new vasculature. Inhibition of angiogenesis, extensively studied in cancer, might therefore be of interest as treatment option for RA. Hypoxia-inducible factor-1 (HIF-1) has been reported to play a critical role in the regulation of hypoxia driven angiogenesis. HIF-1 is a transcription factor that is constitutively expressed in many cells. It gains transcriptional activity in hypoxic cells leading to the expression of genes involved in angiogenesis. The synovium is hypoxic, but also in an inflammatory environment such as seen in RA, inflammatory cytokines may be important inducers of HIF-1 expression and/or activation. Many drugs currently used in the treatment of RA have anti-angiogenic effects, which are exerted at different levels. Blocking of TNF-α, for instance, reduces TNF-α induced VEGF production. Studies aiming at direct inhibition of proangiogenic factors, such as inhibiting VEGF- or FGF-receptor signalling or blocking VEGF by monoclonal anti-VEGF antibody therapeutics, are in progress. Inhibition of HIF-1 expression or activation, either by blocking signal transduction pathways leading to HIF-1 induction or by inhibiting accumulation of HIF -1 protein, represents a new strategy, which is of interest for the treatment of RA. This review will concisely summarize the general knowledge on the molecular control of gene expression by HIF-1, its involvement in RA, and potential for therapeutic intervention at the level of HIF-1 activity.
Keywords: Hypoxia-inducible factor, pharmacology, rheumatoid arthritis, angiogenesis
Current Medicinal Chemistry
Title: Hypoxia-Inducible Factor-1 as Regulator of Angiogenesis in Rheumatoid Arthritis - Therapeutic Implications
Volume: 17 Issue: 3
Author(s): J. Westra, G. Molema and C. G.M. Kallenberg
Affiliation:
Keywords: Hypoxia-inducible factor, pharmacology, rheumatoid arthritis, angiogenesis
Abstract: Angiogenesis plays an important role in the pathogenesis of inflammatory diseases, including rheumatoid arthritis (RA). The site and extent of inflammation and subsequent joint destruction in the rheumatoid synovium is dependent on the development of new vasculature. Inhibition of angiogenesis, extensively studied in cancer, might therefore be of interest as treatment option for RA. Hypoxia-inducible factor-1 (HIF-1) has been reported to play a critical role in the regulation of hypoxia driven angiogenesis. HIF-1 is a transcription factor that is constitutively expressed in many cells. It gains transcriptional activity in hypoxic cells leading to the expression of genes involved in angiogenesis. The synovium is hypoxic, but also in an inflammatory environment such as seen in RA, inflammatory cytokines may be important inducers of HIF-1 expression and/or activation. Many drugs currently used in the treatment of RA have anti-angiogenic effects, which are exerted at different levels. Blocking of TNF-α, for instance, reduces TNF-α induced VEGF production. Studies aiming at direct inhibition of proangiogenic factors, such as inhibiting VEGF- or FGF-receptor signalling or blocking VEGF by monoclonal anti-VEGF antibody therapeutics, are in progress. Inhibition of HIF-1 expression or activation, either by blocking signal transduction pathways leading to HIF-1 induction or by inhibiting accumulation of HIF -1 protein, represents a new strategy, which is of interest for the treatment of RA. This review will concisely summarize the general knowledge on the molecular control of gene expression by HIF-1, its involvement in RA, and potential for therapeutic intervention at the level of HIF-1 activity.
Export Options
About this article
Cite this article as:
Westra J., Molema G. and Kallenberg G.M. C., Hypoxia-Inducible Factor-1 as Regulator of Angiogenesis in Rheumatoid Arthritis - Therapeutic Implications, Current Medicinal Chemistry 2010; 17 (3) . https://dx.doi.org/10.2174/092986710790149783
DOI https://dx.doi.org/10.2174/092986710790149783 |
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
-
Methotrexate in the Treatment of Psoriasis and Rheumatoid Arthritis: Mechanistic Insights, Current Issues and Novel Delivery Approaches
Current Pharmaceutical Design Prerequisite of a Holistic Blend of Traditional and Modern Approaches of Cancer Management
Current Cancer Therapy Reviews Muscle Metabolism and Exercise Capacity in Cachexia
Current Pharmaceutical Design Development of Yeast Molecular Display Systems Focused on Therapeutic Proteins, Enzymes, and Foods: Functional Analysis of Proteins and its Application to Bioconversion
Recent Patents on Biotechnology Interaction of Drug or Food with Drug Transporters in Intestine and Liver
Current Drug Metabolism Functional Components from Nature-Derived Drugs for the Treatment of Rheumatoid Arthritis
Current Drug Targets Serine Protease Inhibitors and T Lymphocyte Immunity
Current Immunology Reviews (Discontinued) Optimization of Drug Safety Profile in Inflammatory Bowel Disease Through a Personalized Approach
Current Drug Targets Flavonoids: Prospective Drug Candidates
Mini-Reviews in Medicinal Chemistry Treatment of Refractory Autoimmune Diseases with Ablative Immunotherapy Using Monoclonal Antibodies and / or High Dose Chemotherapy with Hematopoietic Stem Cell Support
Current Pharmaceutical Design Targeting Complement in Rheumatoid Arthritis
Current Rheumatology Reviews Visfatin: Structure, Function and Relation to Diabetes Mellitus and Other Dysfunctions
Current Medicinal Chemistry Neuromodulatory and Anti-Inflammatory Ingredient for Sensitive Skin: In Vitro Assessment
Inflammation & Allergy - Drug Targets (Discontinued) Nonsteroidal Anti-Inflammatory Drugs: Exploiting Bivalent COXIB/ TP Antagonists for the Control of Cardiovascular Risk
Current Medicinal Chemistry Role of PI3 Kinase Gamma in Excitation-Contraction Coupling and Heart Disease
Cardiovascular & Hematological Disorders-Drug Targets Innate Immunity, Toll-Like Receptors, and Diabetes
Current Immunology Reviews (Discontinued) Chlorogenic Acid Suppresses a Cell Adhesion Molecule in Experimental Autoimmune Myocarditis in Mice
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Interleukin-6 and Lung Inflammation: Evidence for a Causative Role in Inducing Respiratory System Resistance Increments
Inflammation & Allergy - Drug Targets (Discontinued) Humanized Cobra Venom Factor: Experimental Therapeutics for Targeted Complement Activation and Complement Depletion
Current Pharmaceutical Design Targeting the Ubiquitin Proteasome System: Beyond Proteasome Inhibition
Current Pharmaceutical Design