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
-
Extracellular Vesicles as Innovative Tools for Assessing Adverse
Effects of Immunosuppressant Drugs
Current Medicinal Chemistry Clinical Use of Rituximab in Patients with HIV Related Lymphoma and Multicentric Castlemans Disease
Current Drug Delivery Gene Therapy for Arthritis
Current Drug Targets Editorial: Applications of Medicinal Bioinorganic Chemistry
Current Medicinal Chemistry Gene Therapy Approaches for Cartilage Injury and Osteoarthritis
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Are Patient Self-Report Questionnaires as "Scientific" as Biomarkers in "Treat-totarget" and Prognosis in Rheumatoid Arthritis?
Current Pharmaceutical Design Indications of Anti-Inflammatory Drugs in Cardiac Diseases
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry “Something is Wrong in the Ras Kingdom” - Evidence for the Involvement of p21Ras/MAP Kinase in Autoimmune Diseases
Current Rheumatology Reviews Pharmacogenetics in Treatment of Rheumatoid Arthritis
Current Pharmaceutical Design Immune Modulation by Plasmid DNA-mediated Cytokine Gene Transfer
Current Pharmaceutical Design Changes in the Expression Profile of JAK/STAT Signaling Pathway Genes and Mirnas Regulating their Expression Under the Adalimumab Therapy
Current Pharmaceutical Biotechnology Aspirin: from a Historical Perspective
Recent Patents on Cardiovascular Drug Discovery Structural Biology of Recombinant Bovine Pancreatic Phospholipase A2 and its Inhibitor Complexes
Current Topics in Medicinal Chemistry Wealth of Opportunity - The C1 Domain as a Target for Drug Development
Current Drug Targets Natural Compounds and Plant Extracts as Therapeutics Against Chronic Inflammation in Alzheimer's Disease - A Translational Perspective
CNS & Neurological Disorders - Drug Targets Editorial: Pulmonary Involvement in Systemic Disorders
Current Drug Targets - Inflammation & Allergy Role of Kynurenines in the Central and Peripherial Nervous Systems
Current Neurovascular Research Psychosomatic Features, Compliance and Complementary Therapies in Rheumatoid Arthritis
Current Rheumatology Reviews Total Phenolic Content and In vitro Antioxidant Activity of Endophytic Fungi Isolated from Calotropis procera L.
Current Bioactive Compounds The Roles of Antimicrobial Peptides in Innate Host Defense
Current Pharmaceutical Design