Role of Plasminogen System Components in Focal Cerebral Ischemic Infarction

Author:

Nagai N.1,De Mol M.1,Lijnen H. R.1,Carmeliet P.1,Collen D.1

Affiliation:

1. From the Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology (N.N., P.C.), and the Center for Molecular and Vascular Biology (M.D.M., H.R.L., D.C.), KU Leuven, Belgium, and the Department of Physiology, Hamamatsu University School of Medicine, Shizuoka, Japan (N.N.).

Abstract

Background —The role of plasminogen system components in focal cerebral ischemic infarction (FCI) was studied in mice deficient in plasminogen (Plg −/− ), in tissue or urokinase plasminogen activator (tPA −/− or uPA −/− ), or in plasminogen activator inhibitor-1 or α 2 -antiplasmin (PAI-1 −/− or α 2 -AP −/− ). Methods and Results —FCI was produced by ligation of the left middle cerebral artery and measured after 24 hours by planimetry of stained brain slices. In control (wild-type) mice, infarct size was 7.6±1.1 mm 3 (mean±SEM), uPA −/− mice had similar infarcts (7.8±1.0 mm 3 , P =NS), tPA −/− mice smaller (2.6±0.80 mm 3 , P <0.0001), PAI-1 −/− mice larger (16±0.52 mm 3 , P <0.0001), and Plg −/− mice larger (12±1.2 mm 3 , P =0.037) infarcts. α 2 -AP −/− mice had smaller infarcts (2.2±1.1 mm 3 , P <0.0001 versus wild-type), which increased to 13±2.5 mm 3 ( P <0.005 versus α 2 -AP −/− ) after intravenous injection of human α 2 -AP. Injection into α 2 -AP −/− mice of Fab fragments of affinospecific rabbit IgG against human α 2 -AP, after injection of 200 μg human α 2 -AP, reduced FCI from 11±1.5 to 5.1±1.1 mm 3 ( P =0.004). Conclusions —Plg system components affect FCI at 2 different levels: (1) reduction of tPA activity ( tPA gene inactivation) reduces whereas its augmentation ( PAI-1 gene inactivation) increases infarct size, and (2) reduction of Plg activity ( Plg gene inactivation or α 2 -AP injection) increases whereas its augmentation (α 2 - AP gene inactivation or α 2 -AP neutralization) reduces infarct size. Inhibition of α 2 -AP may constitute a potential avenue to treatment of FCI.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

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