Abstract
High molecular weight kininogen (HK) is a plasma protein that is cleaved by plasma kallikrein in the clinical settings of sepsis and chronic inflammatory diseases such as rheumatoid arthritis and Crohns disease. This proteolytic event results in a nonapeptide, bradykinin (BK), and a kinin-free derivative of HK, namely HKa. BK promotes angiogenesis by upregulation of bFGF through the B1 receptor or by stimulation of VEGF formation via the B2 receptor. Kininogen- deficient rats show diminished angiogenesis when neovascularization is stimulated. The formation of HKa results in exposure of domain 5 (D5). HKa or D5 inhibit endothelial cell migration and proliferation, both of which are needed for angiogenesis. In the chicken chorioallantoic membrane assay when neovascularization is stimulated by bFGF or VEGF, HKa or D5 inhibit angiogenesis. Monoclonal antibody C11C1, which prevents binding of HK to endothelial cells, also limits its conversion to BK thus downregulating angiogenesis. In vivo, mAb C11C1 inhibits tumor angiogenesis in mice as well as in experimental inflammatory arthritis and inflammatory bowel disease in Lewis rats. In vitro HKa or D5 inhibits endothelial cell adhesion to vitronectin and fibrinogen, resulting in anokis and apoptosis. The HKa receptor, uPAR, forms a signaling complex containing the integrin αvβ3 or α5β1, caveolin, Src kinase Yes, focal adhesion kinase and paxcillin. HKa physically disrupts the complex by interfering with the binding of vitronectin to uPAR. Both mAb C11C1 and D5 have potential applications for controlling unwanted angiogenesis in inflammation and cancer.
Keywords: Factor XII, prekallikrein, kininogen, urokinase plasminogen activator, bradykinin, kininostatin, vitronectin
Current Pharmaceutical Design
Title: Regulation of Angiogenesis by the Kallikrein-Kinin System
Volume: 12 Issue: 21
Author(s): Robert W. Colman
Affiliation:
Keywords: Factor XII, prekallikrein, kininogen, urokinase plasminogen activator, bradykinin, kininostatin, vitronectin
Abstract: High molecular weight kininogen (HK) is a plasma protein that is cleaved by plasma kallikrein in the clinical settings of sepsis and chronic inflammatory diseases such as rheumatoid arthritis and Crohns disease. This proteolytic event results in a nonapeptide, bradykinin (BK), and a kinin-free derivative of HK, namely HKa. BK promotes angiogenesis by upregulation of bFGF through the B1 receptor or by stimulation of VEGF formation via the B2 receptor. Kininogen- deficient rats show diminished angiogenesis when neovascularization is stimulated. The formation of HKa results in exposure of domain 5 (D5). HKa or D5 inhibit endothelial cell migration and proliferation, both of which are needed for angiogenesis. In the chicken chorioallantoic membrane assay when neovascularization is stimulated by bFGF or VEGF, HKa or D5 inhibit angiogenesis. Monoclonal antibody C11C1, which prevents binding of HK to endothelial cells, also limits its conversion to BK thus downregulating angiogenesis. In vivo, mAb C11C1 inhibits tumor angiogenesis in mice as well as in experimental inflammatory arthritis and inflammatory bowel disease in Lewis rats. In vitro HKa or D5 inhibits endothelial cell adhesion to vitronectin and fibrinogen, resulting in anokis and apoptosis. The HKa receptor, uPAR, forms a signaling complex containing the integrin αvβ3 or α5β1, caveolin, Src kinase Yes, focal adhesion kinase and paxcillin. HKa physically disrupts the complex by interfering with the binding of vitronectin to uPAR. Both mAb C11C1 and D5 have potential applications for controlling unwanted angiogenesis in inflammation and cancer.
Export Options
About this article
Cite this article as:
Colman W. Robert, Regulation of Angiogenesis by the Kallikrein-Kinin System, Current Pharmaceutical Design 2006; 12 (21) . https://dx.doi.org/10.2174/138161206777698710
DOI https://dx.doi.org/10.2174/138161206777698710 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Medicinal and Therapeutic Potential of Herbs and Plant Metabolites / Extracts Countering Viral Pathogens - Current Knowledge and Future Prospects
Current Drug Metabolism Melatonin Synthetic Analogs as Nitric Oxide Synthase Inhibitors
Mini-Reviews in Medicinal Chemistry Vaccination and Rheumatic Diseases: Is There Still a Dilemma?
Current Rheumatology Reviews The Role of MIF in Hepatic Function, Oxidative Stress, and Inflammation in Thioacetamide-induced Liver Injury in Mice: Protective Effects of Betaine
Current Medicinal Chemistry Thioredoxin Reductase and its Inhibitors
Current Protein & Peptide Science High Resolution Molecular Analysis as Tool for Evaluation of Arthritis Pathology
Current Rheumatology Reviews The Role of a Human Hematopoietic Mesenchymal Progenitor in Wound Healing and Fibrotic Diseases and Implications for Therapy
Current Stem Cell Research & Therapy Preface [Hot topic: Autoimmunity (Executive Editors: D. Stahl and W. Sibrowski)]
Current Pharmaceutical Design Natural Compounds and Plant Extracts as Therapeutics Against Chronic Inflammation in Alzheimer's Disease - A Translational Perspective
CNS & Neurological Disorders - Drug Targets Molecular Hydrogen: New Antioxidant and Anti-inflammatory Therapy for Rheumatoid Arthritis and Related Diseases
Current Pharmaceutical Design The Brain-Immune-Gut Triangle: Innate Immunity in Psychiatric and Neurological Disorders
Current Immunology Reviews (Discontinued) Leukocyte Adhesion: A Suitable Target for Anti-Inflammatory Drugs
Current Pharmaceutical Design Lipoxins, The Novel Mediators of Gastroprotection and Gastric Adaptation to Ulcerogenic action of Aspirin
Current Pharmaceutical Design Clinical Approaches Toward Tumor Angiogenesis: Past, Present and Future
Current Pharmaceutical Design Aptamers Against Cell Surface Receptors: Selection, Modification and Application
Current Medicinal Chemistry Synthesis, Characterization, Biological Activity and Voltammetric Behavior and Determination of Cefaclor Metal Complexes
Current Analytical Chemistry Lipoprotein (a) and Cardiovascular Risk: The Show Must go on
Current Medicinal Chemistry Autoimmune Diseases in Gastroenterology
Current Pharmaceutical Design Childhood Systemic Lupus Erythematosus: New and Old Treatments
Current Pediatric Reviews Impact of Traditional Therapies and Biologics on Cardiovascular Diseases in Rheumatoid Arthritis
Current Vascular Pharmacology