Anti-restenotic roles of dihydroaustrasulfone alcohol involved in inhibiting PDGF-BB-stimulated proliferation and migration of vascular smooth muscle cells

Pei Chuan Li, Ming Jyh Sheu, Wei Fen Ma, Chun Hsu Pan, Jyh Horng Sheu, Chieh Hsi Wu

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Dihydroaustrasulfone alcohol (DA), an active compound firstly isolated from marine corals, has been reported to reveal anti-cancer and anti-inflammation activities. These reported activities of DA raised a possible application in anti-restenosis. Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) and the stimulation of platelet-derived growth factor (PDGF)-BB play major pathological processes involved in the development of restenosis. Experimental results showed that DA markedly reduced balloon injury-induced neointima formation in the rat carotid artery model and significantly inhibited PDGF-BB-stimulated proliferation and migration of VSMCs. Our data further demonstrated that translational and active levels of several critical signaling cascades involved in VSMC proliferation, such as extracellular signal-regulated kinase/mitogen-activated protein kinases (ERK/MAPK), phosphatidylinositol 3-kinase (PI3K)/AKT, and signal transducer and activator of transcription (STAT), were obviously inhibited. In addition, DA also decreased the activation and expression levels of gelatinases (matrix metalloproteinase (MMP)-2 and MMP-9) involved in cell migration. In conclusion, our findings indicate that DA can reduce balloon injury-neointimal hyperplasia, the effect of which may be modulated through suppression of VSMC proliferation and migration. These results suggest that DA has potential application as an anti-restenotic agent for the prevention of restenosis.

Original languageEnglish
Pages (from-to)3046-3060
Number of pages15
JournalMarine Drugs
Volume13
Issue number5
DOIs
Publication statusPublished - May 1 2015

Keywords

  • Anti-restenosis
  • Dihydroaustrasulfone alcohol
  • Marine origin
  • Neointimal hyperplasia

ASJC Scopus subject areas

  • Drug Discovery

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