ACTIVATION OF TRANSFORMING GROWTH-FACTOR-BETA IS INHIBITED IN TRANSGENIC APOLIPOPROTEIN(A) MICE

被引：338

作者：

GRAINGER, DJ ^{[1
]}

KEMP, PR ^{[1
]}

LIU, AC ^{[1
]}

LAWN, RM ^{[1
]}

METCALFE, JC ^{[1
]}

机构：

[1] STANFORD UNIV,SCH MED,DIV CARDIOVASC MED,STANFORD,CA 94305

来源：

NATURE | 1994年 / 370卷 / 6489期

基金：

英国惠康基金;

关键词：

D O I：

10.1038/370460a0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A HIGH concentration of serum lipoprotein(a) is a risk factor for atherosclerosis(1-3). Lipoprotein(a) consists of low-density lipoprotein with the additional protein component, apolipoprotein(a), a homologue of plasminogen(4). Lipoprotein(a) and apolipoprotein(a) enhance proliferation of human vascular smooth muscle cells (hVSMCs) in culture by inhibiting activation of plasminogen to plasmin, thus blocking the proteolytic activation of transforming growth factor-beta (TGF-beta)(5), an autocrine inhibitor of hVSMC proliferation(5,6). The hypothesis that this pathway is a key step in atherogenesis(5) is tested on transgenic mice expressing the human apolipoprotein(a) gene. We show here that the activation of TGF-beta is inhibited in the aortic wall and serum of mice expressing apolipoprotein(a), as a consequence of apolipoprotein(a) inhibition of plasminogen activation. These effects are closely correlated with VSMC activation.

引用

页码：460 / 462

页数：3

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