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ADAMTS-7, a novel proteolytic culprit in vascular remodeling

Wang Li, WANG Xian, KONG Wei^*

Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Science of Ministry of Education, Beijing 100191, China

Abstract

Vascular remodeling is being recognized as a fundamental process during atherosclerosis and restenosis. Cumulative studieshave demonstrated that extracellular matrix (ECM) degrading enzymes play a critical role during vascular remodeling. A disintegrin andmetalloproteinase with thrombospondin motifs (ADAMTS) family is a recently identified metalloproteinase family which also hascapacity to degrade ECM. ADAMTS family consists of 19 members and has been linked to a variety of physiological processesincluding development, angiogenesis, coagulation etc. Aberrant expression or function of ADAMTS members have been implicated tomany disease states such as arthritis, cancer, thrombocytopenic purpura, but barely described with regard to cardiovascular disease.This review summarizes the recent advance with respect to the role of ADAMTS-7 in vascular remodeling. We review the structure,tissue distribution, substrate, expression and regulation of ADAMTS-7, especially highlight the fine tune by ADAMTS-7 of itssubstrate cartilage oligomeric matrix protein (COMP) in maintaining vascular homeostasis. By use of rat carotid artery balloon injurymodel to mimic vascular injury in vivo, we found that ADAMTS-7 protein was accumulated preferentially in neointima and mainlylocalized in vascular smooth muscle cells (VSMCs). Adenovirus-elicited ADAMTS-7 overexpression greatly accelerated VSMCsmigration and proliferation both in vivo and in vitro, and subsequently aggravated neointima thickening post-injury. Conversely,siRNA-mediated ADAMTS-7 knock down bona fide inhibited VSMCs migration and proliferation in cultured VSMCs and injuredarteries, and ultimately ameliorated neointima area. Further studies demonstrated that ADAMTS-7 facilitated VSMCs migrationthrough degradation of its substrate COMP. Moreover, we elucidated that COMP has the capacity to maintain the contractilephenotype of VSMCs through interacting with integrin α7β1. ADAMTS-7 may therefore serve as a novel therapeutic target foratherosclerosis and postangioplasty restenosis.

Key words: ADAMTS-7; COMP; vascular smooth muscle; migration; proliferation

Received: 2010-06-08　　Accepted: 2010-07-23

Corresponding author: 孔炜　　E-mail: kongw@bjmu.edu.cn

Citing This Article：

Wang Li, WANG Xian, KONG Wei. ADAMTS-7, a novel proteolytic culprit in vascular remodeling. Acta Physiol Sin 2010; 62 (4): 285-294 (in Chinese with English abstract).