Abstract
Copper promotion of angiogenesis has been known for more than two decades, but the mechanism of action of copper has not been explored until recently. Copper stimulation of factors involved in vessel formation and maturation, such as vascular endothelial growth factor (VEGF), is mainly responsible for its angiogenesis effect. Copper is required for the activation of hypoxia-inducible factor-1 (HIF-1), a major transcription factor regulating the expression of VEGF. Copper would be transported into nucleus by a copper chaperon for superoxide dismutase-1. Copper is required for HIF-1 interaction with the hypoxia-responsive element of the target genes and ensures the formation of HIF-1 transcriptional complex, thus activating the expression of target genes including VEGF. On the other hand, excess copper can stabilize HIF-1α, the rate-limiting component of HIF-1, leading to its accumulation in cytoplasm and thus HIF-1 activation. The essential role of copper in production of VEGF makes it implicated in anti-angiogenesis therapy, such as the application of copper chelators in cancer therapy. However, suppression of angiogenesis is involved in the progression of heart hypertrophy and its transition to heart failure, therefore copper supplementation improves hypertrophic heart disease conditions. This dilemma of copper implications in cancer therapy and heart hypertrophy dictates a comprehensive understanding of a patients condition before an implementation of copper manipulation therapy for different diseases. In this context, a development of diagnosis for copper metabolic changes as well as a tissue-specific copper manipulation would greatly benefit patients with an implication of copper manipulation therapy.
Keywords: Copper, angiogenesis, VEGF, HIF-1, cancer, heart, blood vessel
Current Medicinal Chemistry
Title: Role of Copper in Angiogenesis and Its Medicinal Implications
Volume: 16 Issue: 10
Author(s): Huiqi Xie and Y. James Kang
Affiliation:
Keywords: Copper, angiogenesis, VEGF, HIF-1, cancer, heart, blood vessel
Abstract: Copper promotion of angiogenesis has been known for more than two decades, but the mechanism of action of copper has not been explored until recently. Copper stimulation of factors involved in vessel formation and maturation, such as vascular endothelial growth factor (VEGF), is mainly responsible for its angiogenesis effect. Copper is required for the activation of hypoxia-inducible factor-1 (HIF-1), a major transcription factor regulating the expression of VEGF. Copper would be transported into nucleus by a copper chaperon for superoxide dismutase-1. Copper is required for HIF-1 interaction with the hypoxia-responsive element of the target genes and ensures the formation of HIF-1 transcriptional complex, thus activating the expression of target genes including VEGF. On the other hand, excess copper can stabilize HIF-1α, the rate-limiting component of HIF-1, leading to its accumulation in cytoplasm and thus HIF-1 activation. The essential role of copper in production of VEGF makes it implicated in anti-angiogenesis therapy, such as the application of copper chelators in cancer therapy. However, suppression of angiogenesis is involved in the progression of heart hypertrophy and its transition to heart failure, therefore copper supplementation improves hypertrophic heart disease conditions. This dilemma of copper implications in cancer therapy and heart hypertrophy dictates a comprehensive understanding of a patients condition before an implementation of copper manipulation therapy for different diseases. In this context, a development of diagnosis for copper metabolic changes as well as a tissue-specific copper manipulation would greatly benefit patients with an implication of copper manipulation therapy.
Export Options
About this article
Cite this article as:
Xie Huiqi and Kang James Y., Role of Copper in Angiogenesis and Its Medicinal Implications, Current Medicinal Chemistry 2009; 16 (10) . https://dx.doi.org/10.2174/092986709787846622
DOI https://dx.doi.org/10.2174/092986709787846622 |
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
-
Kinetic Measurement Techniques in the Evaluation of Lipid Metabolism
Current Drug Discovery Technologies Development of Improved Factor VIII Molecules and New Gene Transfer Approaches for Hemophilia A
Current Gene Therapy Hypertension in Egypt: A Systematic Review
Current Hypertension Reviews Approaches to the Management of Acute Kidney Injury in Children
Recent Patents on Biomarkers Pharmacotherapy of Aortic Stenosis-Success or Failure?
Current Pharmaceutical Biotechnology Cervical Cancer Diagnosis: Insights into Biochemical Biomarkers and Imaging Techniques
Combinatorial Chemistry & High Throughput Screening Metabolism-based Drug-drug Interactions in Patients with Chronic Respiratory Diseases: A Review Focusing on Drugs Affecting the Respiratory System
Current Drug Metabolism Editorial (Thematic Issue: Natural Leads in Drug Discovery against Metabolic Disorders and their Related Infectious Diseases)
Current Topics in Medicinal Chemistry Using Bioinformatics Techniques for Gene Identification in Drug Discovery and Development
Current Drug Metabolism Inorganic Nanoparticles for In Vitro Cancer Diagnosis: A Patent Review
Recent Patents on Nanomedicine Zinc and Cell Signaling During Inflammation: Implications in Atherosclerosis
Current Nutrition & Food Science Pyrazolines: A Biological Review
Mini-Reviews in Medicinal Chemistry Novel Drugs and the Response to Hypoxia: HIF Stabilizers and Prolyl Hydroxylase
Recent Patents on Cardiovascular Drug Discovery Beneficial Actions of Polyunsaturated Fatty Acids in Cardiovascular Diseases: But, How and Why?
Current Nutrition & Food Science Subject Index To Volume 4
Cardiovascular & Hematological Agents in Medicinal Chemistry Indications, Implications and Applications of Renal Denervation. Have we Discovered Something new?
Current Hypertension Reviews Pharmacotherapy of Abdominal Aortic Aneurysms
Current Vascular Pharmacology Insulin Therapy for Improving Cardiac Surgical Outcomes
Current Drug Targets Insulin Secretion and Interleukin-1β Dependent Mechanisms in Human Diabetes Remission After Metabolic Surgery
Current Medicinal Chemistry Appropriate Antibiotic Prescribing Pattern in Hospitalized Children
Current Drug Safety