Endothelin-1 induces an increase in total protein synthesis and expression of the smooth muscle alpha-actin gene in vascular smooth muscle cells.

Abstract:

:The growth response of aortic vascular smooth muscle cells (VSMCs) to chronic hypertension includes vascular hypertrophy. We have shown previously that angiotensin II positively regulates the expression of the human vascular smooth muscle (SM) alpha-actin gene. To further expand our understanding of vasoactive peptide-induced vascular hypertrophy, we studied endothelin-1 (ET-1) regulation of total protein synthesis and cytoskeletal gene expression in VSMCs. In a concentration-dependent manner ET-1 increased [3H] leucine incorporation by VSMCs (122.4 +/- 5.5%, mean +/- SEM, n = 5). ET-1 (0.1 microM) induced expression of SM alpha-actin mRNA as detected by Northern blot analysis. Also, ET-1 in a concentration-dependent manner (0.1 nM-0.1 microM) induced expression of the chloramphenicol acetyl transferase gene driven by 896 bp of the human SM alpha-actin promoter when transiently transfected into rat aortic VSMCs by the calcium phosphate method (141.2 +/- 9.8%, mean +/- SEM, n = 10). These data suggest that part of ET-1-induced increase in protein synthesis is achieved through transcriptional regulation of the SM alpha-actin gene via activation of cis-acting element(s) in the promoter. Such findings help elucidate the role of ET-1 in regulation of vascular growth.

journal_name

Life Sci

journal_title

Life sciences

authors

Andrawis NS,Wang E,Abernethy DR

doi

10.1016/0024-3205(96)00332-3

subject

Has Abstract

pub_date

1996-01-01 00:00:00

pages

523-8

issue

7

eissn

0024-3205

issn

1879-0631

pii

0024320596003323

journal_volume

59

pub_type

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