ADAMTS-7 promotes vascular smooth muscle cells proliferation in vitro and in vivo.
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, [(3)H]-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.
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
Lu
L
Zhang
Fang
F
Yu
Li
L
Wang
JinGang
J
Zheng
YaoYao
Y
Du
YaQian
Y
Huang
Bo
B
Liu
Xian
X
Wang
Wei
W
Kong
D051722:ADAM Proteins / Q000235:genetics / Q000502:physiology*; D000071118:ADAMTS7 Protein; D000818:Animals; D049109:Cell Proliferation / Q000502:physiology*; D055785:Gene Knockdown Techniques; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D051722:ADAM Proteins; D000071118:ADAMTS7 Protein; C539627:Adamts7 protein, rat