title: Interference of IP-10 expression inhibits vascular smooth muscle cell proliferation and intimal hyperplasia in carotid artery: a new insight in the prevention of restenosis.
abstract: After vascular angioplasty, vascular smooth muscle cell (VSMC) proliferation causes atherosclerosis and intimal hyperplasia leading to restenosis. Interferon-γ-inducible protein (IP)-10 plays a role in atherogenesis, but the mechanism remains unclear. We evaluated the role of IP-10 in intimal hyperplasia and restenosis. IP-10 expression was determined in arterial specimens from 20 arteriosclerotic obliteration patients and 6 healthy individuals. VSMCs were stimulated in vitro with IFN-γ and transfected with IP-10 siRNA. Silencing was verified with RT-PCR/Western blot; cell proliferation rate was detected by methyl-thiazol-tetrazolium. The carotid artery model of atherosclerosis injury was established with IP-10 siRNA. IP-10 expression was detected at 1 and 4 weeks using RT-PCR and immunohistochemistry. Artery morphology was assessed with hematoxylin-and-eosin staining, and intimal hyperplasia was evaluated by electron microscopy. IP-10 was overexpressed in arteriosclerotic obliteration group compared with control group (P < 0.05). IP-10 expression in transfected group was significantly lower than in untransfected group. The intima-to-media ratio of transfected group at 4 weeks was lower than that of untransfected group (P < 0.01). The transfected group exhibited more regular intimal structure and less hyperplasia under electron microscopy. We, therefore, concluded that IP-10 played an important role in intimal hyperplasia as siRNA-mediated IP-10 silencing inhibited aberrant VSMCs hyperplasia and reduced restenosis.
authors.affiliation: Department of Vascular Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. zuojunhu@hotmail.com
authors.forename: Hu
authors.initials: H
authors.lastname: Zuojun
authors.forename: Hu
authors.initials: H
authors.lastname: Lingyu
authors.forename: He
authors.initials: H
authors.lastname: Wei
authors.forename: Yin
authors.initials: Y
authors.lastname: Henghui
authors.forename: Zhang
authors.initials: Z
authors.lastname: Chonggang
authors.forename: Wang
authors.initials: W
authors.lastname: Jingsong
authors.forename: Wang
authors.initials: W
authors.lastname: Mian
authors.forename: Liu
authors.initials: L
authors.lastname: Yong
authors.forename: Wang
authors.initials: W
authors.lastname: Shenming
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D017536:Carotid Artery, Common / Q000473:pathology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D023903:Coronary Restenosis / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011817:Rabbits; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D034741:RNA, Small Interfering