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

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1524-1533
Number of pages10
JournalJournal of Natural Products
Volume75
Issue number9
DOIs
Publication statusPublished - Sep 28 2012
Externally publishedYes

Fingerprint

Phosphorylation
Balloons
Vascular Smooth Muscle
Smooth Muscle Myocytes
Cell Movement
Muscle
Cells
Matrix Metalloproteinase 9
Phosphatidylinositol 3-Kinases
Tissue Inhibitor of Metalloproteinase-2
Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase Inhibitors
Matrix Metalloproteinase 2
Wounds and Injuries
Cell proliferation
Hyperplasia
hispolon
Assays
Cell Proliferation
Tissue

ASJC Scopus subject areas

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

Cite this

Hispolon attenuates balloon-injured neointimal formation and modulates vascular smooth muscle cell migration via AKT and ERK phosphorylation. / Chien, Yi Chung; Huang, Guang Jhong; Cheng, Hsu Chen; Wu, Chieh Hsi; Sheu, Ming Jyh.

In: Journal of Natural Products, Vol. 75, No. 9, 28.09.2012, p. 1524-1533.

Research output: Contribution to journalArticle

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