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Intravenous clusterin administration reduces myocardial infarct size in rats.

Abstract：

BACKGROUND:Clusterin (Apolipoprotein J), a plasma protein with cytoprotective and complement-inhibiting activities, localizes in the infarcted heart during myocardial infarction (MI). Recently, we have shown a protective effect of exogenous clusterin in vitro on ischaemically challenged cardiomyocytes independent of complement. We therefore hypothesized that intravenous clusterin administration would reduce myocardial infarction damage. METHODS:Wistar rats undergoing experimental MI, induced by 40 min ligation of a coronary vessel, were treated with either clusterin (n=15) or vehicle (n=13) intravenously, for 3 days post-MI. After 4 weeks, hearts were analysed. The putative role of megalin, a clusterin receptor, was also studied. RESULTS:Administration of human clusterin significantly reduced both infarct size (with 75 ± 5%) and death of animals (23% vehicle group vs. 0% clusterin group). Importantly, histochemical analysis showed no signs of impaired wound healing in the clusterin group. In addition, significantly increased numbers of macrophages were found in the clusterin group. We also found that the clusterin receptor megalin was present on cardiomyocytes in vitro which, however, was not influenced by ischaemia. Human clusterin co-localized with this receptor in vitro, but not in the human heart. In addition, using a megalin inhibitor, we found that clusterin did not exert its protective effect on cardiomyocytes through megalin. CONCLUSIONS:Our results thus show that clusterin has a protective effect on cardiomyocytes after acute myocardial infarction in vivo, independent of its receptor megalin. This indicates that clusterin, or a clusterin derivate, is a potential therapeutic agent in the treatment of MI.

journal_name

Eur J Clin Invest

journal_title

European journal of clinical investigation

authors

Van Dijk A,Vermond RA,Krijnen PA,Juffermans LJ,Hahn NE,Makker SP,Aarden LA,Hack E,Spreeuwenberg M,van Rossum BC,Meischl C,Paulus WJ,Van Milligen FJ,Niessen HW

doi

10.1111/j.1365-2362.2010.02345.x

subject

Has Abstract

pub_date

2010-10-01 00:00:00

pages

893-902

issue

10

eissn

0014-2972

issn

1365-2362

journal_volume

40

pub_type

杂志文章

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