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Updated: Jun 8, 2026
Histological Quantification of Chronic Myocardial Infarct in Rats
Published on: December 11, 2016
Intravenous clusterin administration reduces myocardial infarct size in rats
Annemieke Van Dijk1, Rob A Vermond, Paul A J Krijnen
1Department of Pathology, VU Medical Center, Amsterdam, The Netherlands. Annemieke.vandijk@vumc.nl
Insights
Intravenous clusterin administration significantly reduced myocardial infarction (MI) size and mortality in rats. This cytoprotective protein shows therapeutic potential for treating heart attacks, independent of the megalin receptor.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Biochemistry
Background:
- Clusterin (Apolipoprotein J) is a plasma protein with known cytoprotective and complement-inhibiting properties.
- It is found in the infarcted heart during myocardial infarction (MI).
- Previous in vitro studies demonstrated clusterin's protective effect on cardiomyocytes against ischemic stress, independent of complement activation.
Purpose of the Study:
- To investigate the therapeutic potential of intravenous clusterin administration in reducing myocardial infarction damage in vivo.
- To explore the role of the clusterin receptor, megalin, in clusterin's cardioprotective effects.
Main Methods:
- Experimental myocardial infarction was induced in Wistar rats via coronary artery ligation.
- Rats received intravenous clusterin or vehicle for 3 days post-MI.
- Hearts were analyzed after 4 weeks, with additional in vitro studies on cardiomyocytes and the megalin receptor.
Main Results:
- Clusterin administration significantly reduced infarct size by 75% and prevented all mortality.
- No impaired wound healing was observed in the clusterin group.
- Clusterin increased macrophage numbers and exerted its protective effect independently of the megalin receptor.
Conclusions:
- Clusterin demonstrates a significant protective effect on cardiomyocytes following acute myocardial infarction in vivo.
- This effect is independent of the clusterin receptor, megalin.
- Clusterin or its derivatives represent promising therapeutic agents for myocardial infarction treatment.
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.
