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
-
New Insights in Research About Acute Ischemic Myocardial Injury and Inflammation
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Adding to the Mix: Fibroblast Growth Factor and Platelet-Derived Growth Factor Receptor Pathways as Targets in Non – small Cell Lung Cancer
Current Cancer Drug Targets Editorial (Hot Topic: Antioxidant Heterocyclic Compounds in Drug Discovery and Medicinal Chemistry)
Mini-Reviews in Medicinal Chemistry Delivery Systems for Antimicrobial Peptides and Proteins: Towards Optimization of Bioavailability and Targeting
Current Pharmaceutical Biotechnology Granulocyte Apoptosis and Macrophage Clearance of Apoptotic Cells as Targets for Pharmacological Intervention in Inflammatory Diseases
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Genomics of Chronic Obstructive Pulmonary Disease (COPD); Exploring the SNPs of Protease-Antiprotease Pathway
Current Genomics Protease Inhibitors in the Clinic
Medicinal Chemistry Targeting IAPs as An Approach to Anti-Cancer Therapy
Current Topics in Medicinal Chemistry Adult Stem Cells in Bone and Cartilage Tissue Engineering
Current Stem Cell Research & Therapy Good Uptake of the COVID-19 Vaccine among Patients with Rheumatic Diseases in the United Arab Emirates (UAE)
New Emirates Medical Journal Circulating miR-10a as Predictor of Therapy Response in Rheumatoid Arthritis Patients Treated with Methotrexate
Current Pharmaceutical Biotechnology Musculoskeletal Adverse Drug Reactions: A Review of Literature and Data from ADR Spontaneous Reporting Databases
Current Drug Safety Comparative Molecular Characterization to Reveal Surface Behaviour of Non-proteolytic Bromelain Mutants
Current Pharmaceutical Biotechnology Synthesis and Antioxidant Activity of Indole Derivatives Containing 4-Substituted Piperazine Moieties
Letters in Drug Design & Discovery Preface [Hot Topic: Perspective on VLA-4 Antagonists (Guest Editor: Jefferson W. Tilley)]
Current Topics in Medicinal Chemistry Selectivity, Binding Affinity, and Ionization State of Matrix Metalloproteinase Inhibitors
Current Pharmaceutical Design Natural Triterpenoids and their Derivatives with Pharmacological Activity Against Neurodegenerative Disorders
Mini-Reviews in Organic Chemistry Hypoxia as an Initiator of Neuroinflammation: Microglial Connections
Current Neuropharmacology Dihydrofolate Reductase Gene Variations in Susceptibility to Disease and Treatment Outcomes
Current Genomics Patent Selections
Recent Patents on Inflammation & Allergy Drug Discovery