ADAMTS-7 promotes vascular smooth muscle cells proliferation in vitro and in vivo

作者：Zhang Lu; Yu Fang; Wang Li; Zheng JinGang; Du YaoYao; Huang YaQian; Liu Bo; Wang Xian; Kong Wei^*

来源：Science China Life Sciences, 2015, 58(7): 674-681.

DOI：10.1007/s11427-015-4843-2

• vascular smooth muscle cell
• ADAMTS-7
• proliferation

Vascular smooth muscle cell (VSMC) proliferation and migration are pivotal for the pathogenesis of atherosclerosis and post-angioplasty restenosis. We have recently reported that a disintegrin and metalloproteinase with thrombospondin motifs-7 (ADAMTS-7), a novel metalloproteinase, contributes directly to neointima formation by mediating VSMC migration. However, whether ADAMTS-7 affects VSMC proliferation remains unclear. In this study, we found that luminal adenoviral delivery of ADAMTS-7 aggravated intimal hyperplasia 7 d after injury, paralleled by an increased percentage of PCNA-positive cells in both intima and media. In contrast, perivascular administration of ADAMTS-7 siRNA, but not scrambled siRNA to injured arteries attenuated intimal thickening at day 7, paralleled with reduced intimal VSMC replication, without alteration of VSMC proliferation in the media. In accordance, [H-3]-thymidine incorporation assay in primary cultured rat VSMCs revealed an enhanced replication rate (by 61%) upon ADAMTS-7 overexpression and retarded proliferation (by 23%) upon ADAMTS-7 siRNA administration. Our data demonstrates that ADAMTS-7 promotes VSMC proliferation both in vitro and in vivo. ADAMTS-7 may therefore serve as a novel therapeutic target for atherosclerosis and post-angioplasty restenosis.

• 出版日期2015-7
• 单位中日友好医院; 北京大学