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 |
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頁(從 - 到) | 1524-1533 |
頁數 | 10 |
期刊 | Journal of Natural Products |
卷 | 75 |
發行號 | 9 |
DOIs | |
出版狀態 | 已發佈 - 9月 28 2012 |
對外發佈 | 是 |
ASJC Scopus subject areas
- 補充和替代醫學
- 分子醫學
- 有機化學
- 分析化學
- 藥學科學
- 藥理
- 藥物發現