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Anti-Restenotic Roles of Dihydroaustrasulfone Alcohol Involved in Inhibiting PDGF-BB-Stimulated Proliferation and Migration of Vascular Smooth Muscle Cells

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Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA
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School of Pharmacy, China Medical University, Taichung 404, Taiwan
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School of Nursing, China Medical University, Taichung 404, Taiwan
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Department of Pharmacy, Taipei Medical University, Taipei 110, Taiwan
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Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editor: Peer B. Jacobson
Mar. Drugs 2015, 13(5), 3046-3060; https://doi.org/10.3390/md13053046
Received: 1 February 2015 / Revised: 3 May 2015 / Accepted: 5 May 2015 / Published: 15 May 2015
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. View Full-Text
Keywords: dihydroaustrasulfone alcohol; anti-restenosis; neointimal hyperplasia; marine origin dihydroaustrasulfone alcohol; anti-restenosis; neointimal hyperplasia; marine origin
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Li, P.-C.; Sheu, M.-J.; Ma, W.-F.; Pan, C.-H.; Sheu, J.-H.; Wu, C.-H. Anti-Restenotic Roles of Dihydroaustrasulfone Alcohol Involved in Inhibiting PDGF-BB-Stimulated Proliferation and Migration of Vascular Smooth Muscle Cells. Mar. Drugs 2015, 13, 3046-3060.

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