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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Berberine Inhibits the Gene Expression and Production of Proinflammatory Cytokines by Mononuclear Cells in Rheumatoid Arthritis and Healthy Individuals
Current Rheumatology Reviews Methotrexate in the Treatment of Psoriasis and Rheumatoid Arthritis: Mechanistic Insights, Current Issues and Novel Delivery Approaches
Current Pharmaceutical Design Trends in the Exploration of Anticancer Targets and Strategies in Enhancing the Efficacy of Drug Targeting
Current Molecular Pharmacology A Timely Review of State-of-the-Art Chronopharmaceuticals Synchronized with Biological Rhythms
Current Drug Delivery Preclinical Profile of Bacopasides From Bacopa monnieri (BM) As An Emerging Class of Therapeutics for Management of Chronic Pains
Current Medicinal Chemistry Automated Parallel Solid-Phase Synthesis of Non-Peptide CCR1 Receptor Antagonists
Combinatorial Chemistry & High Throughput Screening Circulating MicroRNAs as Biomarkers for Inflammatory Diseases
MicroRNA The Biology of p38 Kinase: A Central Role in Inflammation
Current Topics in Medicinal Chemistry Modular Nanotransporters for Targeted Intracellular Delivery of Drugs: Folate Receptors as Potential Targets
Current Pharmaceutical Design Biosimilars: From Extrapolation into Off Label Use
Current Pharmaceutical Design Fragment Pharmacophore-Based Screening: An Efficient Approach for Discovery of New Inhibitors of Toll-Like Receptor 5
Combinatorial Chemistry & High Throughput Screening Pleural Involvement in Systemic Disorders
Current Drug Targets - Inflammation & Allergy Management of Connective Tissue Interstitial Lung Disease
Current Respiratory Medicine Reviews Gene Transfer to the Central Nervous System: Current State of the Art of the Viral Vectors
Current Genomics Regenerative Potential of Stem Cells Derived from Human Exfoliated Deciduous (SHED) Teeth during Engineering of Human Body Tissues
Current Stem Cell Research & Therapy Mechanisms of Salt-Sensitive Hypertension
Current Hypertension Reviews Haematopoietic Stem Cell Gene Therapy to Treat Autoimmune Disease
Current Stem Cell Research & Therapy Patent Selections:
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Lactoferrin as a Natural Immune Modulator
Current Pharmaceutical Design The Relationship Between Dietary Lipids and Serum Visfatin and Adiponectin Levels in Postmenopausal Women
Endocrine, Metabolic & Immune Disorders - Drug Targets