Inhibition of protein synthesis and antiproliferative effect of the angiotensin converting enzyme inhibitor trandolaprilat in rat vascular smooth muscle cells
作者:
Yoshio Uehara,
Atsushi Numabe,
Yukari Kawabata,
Satoru Takada,
Nobuhito Hirawa,
Taiji Nagata,
Toshio Ikeda,
Shigeru Yagi,
Masao Omata,
期刊:
Journal of Hypertension
(OVID Available online 1993)
卷期:
Volume 11,
issue 10
页码: 1073-1081
ISSN:0263-6352
年代: 1993
出版商: OVID
关键词: Angiotensin converting enzyme inhibitor;vascular smooth muscle cell;cell proliferation;protein synthesis;actin
数据来源: OVID
摘要:
Objective:To investigate the effect of the angiotensin converting enzyme (ACE) inhibitor trandolaprilat on vascular smooth muscle cell growth, and to analyse its mechanism of action.Design:Aortic vascular smooth muscle cells (VSMC) from Wistar—Kyoto rats were cultured, and cell proliferation was analysed using a cell synchrony technique.Methods:Proliferative activity was assessed by [3H]-thymidine uptake and doubling time. Protein synthesis was assessed by [3H]-leucine incorporation. Actin formation was measured using sodium dodecylsulphate—polyacrylamide slab gel electrophoresis and a densitometric assay. The effect of trandolaprilat on translational protein synthesis was also examined using the cell-free protein synthesis system of reticulocyte lysate and messenger RNA from VSMC.Results:Trandolaprilat decreased [3H]-thymidine uptake and increased the doubling time of randomly cycling VSMC. The cell synchrony study revealed that this antiproliferative effect was due to increased transition time from S to G2-M. Decreased cell cycle progression during G2-M was reflected by inhibition of cellular protein synthesis during this period. Cellular protein in randomly cycling VSMC was also decreased by trandolaprilat. This decreased protein synthesis was probably produced by inhibition of RNA translation.Conclusions:The ACE inhibitor trandolaprilat reduces VSMC proliferation by lengthening the G2-M phase of the cell cycle, and produces a decrease in cellular protein content. This effect is probably mediated by inhibition of protein synthesis at the translational level.
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