title: Anti-Restenotic Roles of Dihydroaustrasulfone Alcohol Involved in Inhibiting PDGF-BB-Stimulated Proliferation and Migration of Vascular Smooth Muscle Cells.
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.
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA. lipeichu@usc.edu.|School of Pharmacy, China Medical University, Taichung 404, Taiwan. lipeichu@usc.edu.
authors.forename: Pei-Chuan
authors.initials: PC
authors.lastname: Li
authors.affiliation: School of Pharmacy, China Medical University, Taichung 404, Taiwan. soybean13mtdtw@gmail.com.
authors.forename: Ming-Jyh
authors.initials: MJ
authors.lastname: Sheu
authors.affiliation: School of Nursing, China Medical University, Taichung 404, Taiwan. lhdaisy@mail.cmu.edu.tw.
authors.forename: Wei-Fen
authors.initials: WF
authors.lastname: Ma
authors.affiliation: Department of Pharmacy, Taipei Medical University, Taipei 110, Taiwan. panch@tmu.edu.tw.
authors.forename: Chun-Hsu
authors.initials: CH
authors.lastname: Pan
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804, Taiwan. sheu@mail.nsysu.edu.tw.
authors.forename: Jyh-Horng
authors.initials: JH
authors.lastname: Sheu
authors.affiliation: School of Pharmacy, China Medical University, Taichung 404, Taiwan. chhswu@tmu.edu.tw.|Department of Pharmacy, Taipei Medical University, Taipei 110, Taiwan. chhswu@tmu.edu.tw.
authors.forename: Chieh-Hsi
authors.initials: CH
authors.lastname: Wu
mesh_terms: D000818:Animals; D000077214:Becaplermin; D002074:Butanones / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D023903:Coronary Restenosis / Q000188:drug therapy* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D058426:Neointima / Q000188:drug therapy / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013450:Sulfones / Q000494:pharmacology*
chemical_list: D002074:Butanones; D020574:Proto-Oncogene Proteins c-sis; D050791:STAT Transcription Factors; D013450:Sulfones; C000590752:dihydroaustrasulfone alcohol; D000077214:Becaplermin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: anti-restenosis; dihydroaustrasulfone alcohol; marine origin; neointimal hyperplasia