Upregulation of Basement Membrane–Degrading Metalloproteinase Secretion After Balloon Injury of Pig Carotid Arteries

Author:

Southgate Kay M.1,Fisher Michael1,Banning Adrian P.1,Thurston Valerie J.1,Baker Andrew H.1,Fabunmi Rosalind P.1,Groves Peter H.1,Davies Malcolm1,Newby Andrew C.1

Affiliation:

1. the Bristol Heart Institute (K.M.S., A.H.B., A.C.N.), University of Bristol, Bristol (UK) Royal Infirmary, and the Departments of Pharmacology (M.F.) and Cardiology (A.P.B., V.J.T., R.P.F., P.H.G.) and the Institute of Nephrology (M.D.), University of Wales College of Medicine, Heath Park Cardiff.

Abstract

Basement membrane–degrading metalloproteinases (gelatinases) appear necessary for vascular smooth muscle cell migration and proliferation in culture and for intimal migration of cells after balloon injury to the rat carotid artery. We investigated in the present study the secretion of gelatinases from pig carotid artery tissue after balloon injury. Segments of injured artery and segments proximal and distal to the area of injury were removed 3, 7, and 21 days after balloon dilatation. Medial explants from these segments were then cultured for 3 days, and the serum-free conditioned media were subjected to gelatin zymography. Production of 72- and 95-kD gelatinases was quantified by densitometry. Balloon-injured segments secreted significantly more 72- and 95-kD gelatinase than did paired distal segments at all time points. Release of both gelatinase activities was increased at 3 and 7 days relative to segments from uninjured arteries but declined again by 21 days after balloon injury. Similar results were found for gelatinase levels in extracts of arterial tissue. Consistent with the protein secretion data, in situ hybridization demonstrated that the mRNAs for both gelatinases were upregulated after balloon injury. Expression was prominent in medial smooth muscle cells, particularly around foci of necrosis, and in neointimal cells 3 and 7 days after balloon injury; 72-kD gelatinase mRNA persisted after 21 days and was prominent in regrown endothelial cells. The upregulation of gelatinase activity paralleled the time course of smooth muscle cell migration and proliferation in this model. We conclude that increased gelatinase production occurs in response to balloon injury and may play a role in permitting migration and proliferation of vascular smooth muscle cells.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine,Physiology

Reference45 articles.

1. Clowes AW, Reidy MA, Clowes MM. Kinetics of cellular proliferation after arterial injury: smooth muscle growth in the absence of endothelium. Lab Invest.. 1983;49:327-333.

2. Clowes AW, Clowes MM, Reidy MA. Kinetics of cellular proliferation after arterial injury, III: endothelial and smooth muscle growth in chronically denuded vessels. Lab Invest.. 1986;54:295-303.

3. Waller BF Pinkerton CA Orr CM Slack JD VanTassel JW Peters T. Restenosis 1 to 24 months after clinically successful coronary balloon angioplasty: a necropsy study of 20 patients. J Am Coll Cardiol. 1991;17(suppl B):58B-70B.

4. Ross R. Growth factors in the pathogenesis of atherosclerosis. Acta Med Scand. 1987;715(suppl):33-38.

5. Proposed roles for growth factors in mediating smooth muscle proliferation in vascular pathologies

Cited by 127 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3