Caveolin-1 inhibits matrix metalloproteinase-2 activity in the heart

被引：66

作者：

Chow, A. K.

Cena, J.

El-Yazbi, A. F.

Crawford, B. D.

Holt, A.

Cho, W. J.

Daniel, E. E.

Schulz, R. ^{[1
]}

机构：

[1] Univ Alberta, Cardiovasc Res Grp, Heritage Med Res Ctr 462, Dept Pediat, Edmonton, AB T6G 2S2, Canada

[2] Univ Alberta, Cardiovasc Res Grp, Heritage Med Res Ctr 462, Dept Pharmacol, Edmonton, AB T6G 2S2, Canada

来源：

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY | 2007年 / 42卷 / 04期

基金：

加拿大健康研究院;

关键词：

matrix metalloproteinase; caveolin-1; caveolae; lipid raft; caveolin scaffolding domain; gelatinase; knockout mouse; ISCHEMIA-REPERFUSION INJURY; MYOCARDIAL-ISCHEMIA; SCAFFOLDING DOMAIN; ENDOTHELIAL-CELLS; TISSUE INHIBITOR; IV COLLAGENASE; IN-VIVO; ACTIVATION; PROTEIN; BINDING;

D O I：

10.1016/j.yjmcc.2007.01.008

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Apart from its ability to degrade extracellular matrix proteins, matrix metalloproteinase-2 (MMP-2) was recently revealed to have targets and actions within the cardiac myocyte. The localization of MMP-2 in caveolae of endothelial cells suggests that caveolin-1 (Cav-1) may play a role in regulating MMP-2. The caveolin scaffolding domain (CSD) of Cav-1 regulates several proteins including those involved with signaling cascades. Whether Cav-1 is responsible for regulating MMP-2 in the heart is unknown. Hearts from Cav1(-/-) or Cav-1(+/+) mice were isolated and heart extracts or lipid raft enriched membrane fractions were prepared. MMP-2 activity in Cav-1(-/-) hearts was markedly enhanced when compared with Cav-1(+/+) hearts with no changes in MMP-2 protein levels between groups. In contrast, MMP-2 activity and protein level were greatly reduced in lipid raft enriched fractions of Cav-1(-/-) hearts. Purified CSD inhibited MMP-2 activity in a concentration-dependent manner as assessed using an in vitro degradation assay with a fluorogenic MMP-2 substrate (OmniMMP). These data suggest that Cav-1 plays a role in regulating MMP-2 activity. Cav-1 may thus be a novel mechanism to regulate MMP-2 activity in the heart. (c) 2007 Elsevier Inc. All rights reserved.

引用

页码：896 / 901

页数：6

共 27 条

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