Hispolon attenuates balloon-injured neointimal formation and modulates vascular smooth muscle cell migration via AKT and ERK phosphorylation

Yi Chung Chien, Guang Jhong Huang, Hsu Chen Cheng, Chieh Hsi Wu, Ming Jyh Sheu

研究成果: 雜誌貢獻文章

10 引文 斯高帕斯(Scopus)

摘要

The pathological mechanism of restenosis is attributed primarily to excessive proliferation and migration of vascular smooth muscle cells (VSMC). The preventive effects of hispolon (1) on balloon injury-induced neointimal formation were investigated, and 1 showed potent activity in inhibiting fetal bovine serum-induced VSMC outgrowth. Hispolon (1) significantly inhibited VSMC migration, as shown by trans-well assays. Compound 1 decreased the expression and secretion of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The expression of the endogenous inhibitors of these proteins, namely, tissue inhibitors of MMP (TIMP-1 and TIMP-2), increased. The inhibition by noncytotoxic doses of 1 of VSMC migration was through its negative regulatory effects on FAK phosphorylation, ERK1/2 phosphorylation, and PI3K/AKT. These results demonstrate that 1 can inhibit the migration of VSMC by reduced expression of MMP-9 through the suppression of the FAK signaling pathway and of the activity of PI3K/AKT. The data obtained suggest that 1 might block balloon injury-induced neointimal hyperplasia via the inhibition of VSMC proliferation and migration, without inducing apoptosis.

原文英語
頁(從 - 到)1524-1533
頁數10
期刊Journal of Natural Products
75
發行號9
DOIs
出版狀態已發佈 - 九月 28 2012
對外發佈Yes

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ASJC Scopus subject areas

  • Complementary and alternative medicine
  • Molecular Medicine
  • Organic Chemistry
  • Analytical Chemistry
  • Pharmaceutical Science
  • Pharmacology
  • Drug Discovery

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