[Endothelin-1 production and its involvement in cardiovascular diseases].

Abstract

Endothelin (ET) has been implicated in the pathogenesis of several cardiovascular disorders because of its powerful vasoconstrictor and growth-promoting properties. The ET family consists of three isoforms, ET-1, ET-2 and ET-3. ET-1 appears to be the predominant member of the family generated by vascular endothelial cells. In view of the multiple cardiovascular actions of ET-1, there has been much interest in its contribution to the pathophysiology of hypertension and arteriosclerosis. We have been investigating the roles of ET(A) and ET(B) receptors in ET-1-related cardiovascular diseases using subtype-selective ET receptor antagonists and ET(B) receptor-deficient animals. Our studies have demonstrated that ET-1 overproduction and ET(A)-mediated ET-1 actions seem to play a crucial role in the development of several types of hypertensive and post-ischemic diseases. On the other hand, ET-1 biosynthesis and release are regulated at the transcriptional level, and various endogenous substances are known to stimulate ET-1 gene expression by DNA binding of transcription factors. We and others have recently demonstrated that nuclear factor-kappaB (NF-kappaB), a transcription factor with a pivotal role in inducing genes involved in immune, inflammatory and stress responses, is responsible for endothelial ET-1 production. In in vivo studies, agents that can inhibit the NF-kappaB activation improved the development of ET-1-related cardiovascular diseases. Thus, NF-kappaB inhibition may be a pertinent treatment for ET-1 related diseases.

• Authors: Mamoru Ohkita, Masanori Takaoka, Yasuo Matsumura
• Journal: Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan (Yakugaku Zasshi) Vol. 127 Issue 9 Pg. 1319-29 (Sep 2007) ISSN: 0031-6903 [Print] Japan
• PMID: 17827914 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Endothelin A Receptor Antagonists
• Endothelin-1
• NF-kappa B
• Receptor, Endothelin A
• Nitric Oxide

Topics

• Acute Kidney Injury (drug therapy, etiology)
• Animals
• Cardiovascular Diseases (drug therapy, etiology)
• Endothelin A Receptor Antagonists
• Endothelin-1 (biosynthesis, genetics, physiology)
• Endothelium, Vascular (metabolism)
• Gene Expression Regulation
• Humans
• Hypertension (drug therapy, etiology)
• NF-kappa B (antagonists & inhibitors, physiology)
• Nitric Oxide (physiology)
• Receptor, Endothelin A (physiology)