Abstract
A proteasome-dependent proteolytic pathway serves important functions in cell cycle control and transcriptional regulation; however, its pathophysiological role in cardiovascular diseases is still unclear. We have recently obtained evidence that proteasome inhibitors are capable of preventing the development of deoxycorticosterone acetate (DOCA)-salt-induced hypertension or hypertrophy and of ischemic acute renal failure (ARF). Beneficial effects of the proteasome inhibitors were accompanied by a decrease in endothelin-1 (ET-1) content in the aorta and kidney of DOCA-salt and ischemic ARF animals, respectively. In addition, there is evidence showing that the reduction of nuclear factor-kB (NF-kB) activation is involved in the mechanisms for suppressive effects of proteasome inhibitors on ET-1 gene transcription and the consequent decrease in ET-1 mRNA expression in the cultured vascular endothelial cells. These findings suggest that a proteasome-dependent proteolytic pathway has a crucial role in the pathogenesis of ET-1-related cardiovascular diseases, probably through the activation of NF-kB, and also that the use of proteasome inhibitors may be a novel approach to the treatment of cardiovascular diseases.
Keywords: proteasome, endothelin-1, hypertension, hypertrophy, acute renal failure
Current Vascular Pharmacology
Title: Pathophysiological Role of Proteasome-Dependent Proteolytic Pathway in Endothelin-1-Related Cardiovascular Diseases
Volume: 1 Issue: 1
Author(s): M. Takaoka, M. Ohkita and Y. Matsumura
Affiliation:
Keywords: proteasome, endothelin-1, hypertension, hypertrophy, acute renal failure
Abstract: A proteasome-dependent proteolytic pathway serves important functions in cell cycle control and transcriptional regulation; however, its pathophysiological role in cardiovascular diseases is still unclear. We have recently obtained evidence that proteasome inhibitors are capable of preventing the development of deoxycorticosterone acetate (DOCA)-salt-induced hypertension or hypertrophy and of ischemic acute renal failure (ARF). Beneficial effects of the proteasome inhibitors were accompanied by a decrease in endothelin-1 (ET-1) content in the aorta and kidney of DOCA-salt and ischemic ARF animals, respectively. In addition, there is evidence showing that the reduction of nuclear factor-kB (NF-kB) activation is involved in the mechanisms for suppressive effects of proteasome inhibitors on ET-1 gene transcription and the consequent decrease in ET-1 mRNA expression in the cultured vascular endothelial cells. These findings suggest that a proteasome-dependent proteolytic pathway has a crucial role in the pathogenesis of ET-1-related cardiovascular diseases, probably through the activation of NF-kB, and also that the use of proteasome inhibitors may be a novel approach to the treatment of cardiovascular diseases.
Export Options
About this article
Cite this article as:
Takaoka M., Ohkita M. and Matsumura Y., Pathophysiological Role of Proteasome-Dependent Proteolytic Pathway in Endothelin-1-Related Cardiovascular Diseases, Current Vascular Pharmacology 2003; 1 (1) . https://dx.doi.org/10.2174/1570161033386637
DOI https://dx.doi.org/10.2174/1570161033386637 |
Print ISSN 1570-1611 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6212 |
Call for Papers in Thematic Issues
Ischemic Cardiovascular Diseases: Mechanisms, Diagnosis and Therapy
Ischemic cardiovascular disease includes myocardial infarction, coronary atherosclerotic heart disease, angina pectoris, etc., constitute the leading cause of patient mortality by preventing tissues from getting sufficient oxygen and nutrients. Ischemic heart disease, as a clinical condition, is characterized by myocardial ischemia, causing an imbalance between myocardial blood supply and demand, ...read more
TREATMENT OF CARDIOVASCULAR DISEASE IN CHRONIC AND END STAGE KIDNEY DISEASE
Cardiovascular disease still remains the leading cause of death in Chronic and End Stage Kidney Disease, accounting for more than half of all deaths in dialysis patients. During the past decade, research has been focused on novel therapeutic agents that might delay or even reverse cardiovascular disease and vascular calcification, ...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
-
Biomarkers in Atrial Fibrillation and Heart Failure
Current Medicinal Chemistry Serum Specific Vasopressin-Degrading Activity is Related to Blood Total Cholesterol Levels in Men but not in Women
Medicinal Chemistry Changes in Phenolic Compounds Profiles in Tea Extracts and the Composition of these Phenolic Compounds in Yogurt
Recent Patents on Food, Nutrition & Agriculture Kinetic Measurement Techniques in the Evaluation of Lipid Metabolism
Current Drug Discovery Technologies Toxicities of Immunosuppressive Treatment of Autoimmune Neurologic Diseases
Current Neuropharmacology Virus-Associated Vasculitides
Current Immunology Reviews (Discontinued) Endothelial Dysfunction, Obesity and Insulin Resistance
Current Vascular Pharmacology Obesity Therapy: How and Why?
Current Medicinal Chemistry Parental Hypertension and Cardiovascular Reactivity in Young Adults
Vascular Disease Prevention (Discontinued) MRI of Pancreas in Patients with Chronic Pancreatitis and Healthy Volunteers: Can Pancreatic Signal Intensity and Contrast Enhancement Patterns be Valuable Predictors of Early Chronic Pancreatitis?
Current Medical Imaging Cardiovascular Effects of Flavonoids
Current Medicinal Chemistry Advanced Glycation End Products (AGEs) and their Involvement in Liver Disease
Current Pharmaceutical Design Neuropeptides and Gastric Mucosal Homeostasis
Current Topics in Medicinal Chemistry Body Mass Index (BMI) and Cognitive Functions in Later Life
Current Alzheimer Research Synthesis and Cytotoxic Evaluation for Some New Dihydropyrimidinone Derivatives for Anticancer Activity
Letters in Drug Design & Discovery Cerebral Microbleeds Do Not Predict Hemorrhagic Transformation in Acute Ischemic Stroke Patients with Atrial Fibrillation and/or Rheumatic Heart Disease
Current Neurovascular Research A New Potent NS5A Inhibitor in the Management of Hepatitis C Virus: Ravidasvir
Current Drug Discovery Technologies Visual Spatial Attention Training Improve Spatial Attention and Motor Control for Unilateral Neglect Patients
CNS & Neurological Disorders - Drug Targets Central Nervous System Manifestations in Systemic Lupus Erythematosus
Current Rheumatology Reviews Adiponectin and its Role in Cardiovascular Diseases
Cardiovascular & Hematological Disorders-Drug Targets