Pathophysiological Role of Proteasome-Dependent Proteolytic Pathway in Endothelin-1-Related Cardiovascular Diseases

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.

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