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.
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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 |
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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
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