Effects of cannabinoid receptor type 2 on endogenous myocardial regeneration by activating cardiac progenitor cells in mouse infarcted heart

Jan 17, 2014Science China. Life sciences

Cannabinoid receptor type 2 may help heart repair by activating heart stem cells after a heart attack in mice

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Abstract

CB2 receptor agonist AM1241 can significantly increase cardiac progenitor cells in ischemic myocardium.

Activation of CB2 receptors is associated with improved proliferation of cardiac progenitor cells.
AM1241 treatment decreased serum levels of malondialdehyde, tumor necrosis factor-alpha, and interleukin-6 after myocardial infarction.
Enhanced cardiac function was observed through improved left ventricular ejection fraction and reduced fibrosis after AM1241 administration.
The treatment increased levels of phosphorylated Akt and the expression of heme oxygenase-1.
Activation of the Nrf-2 pathway was promoted by AM1241, but was blocked by the PI3K inhibitor wortmannin.

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Cannabinoid receptor type 2 (CB2) activation is recently reported to promote proliferation of some types of resident stem cells (e.g., hematopoietic stem/progenitor cell or neural progenitor cell). Resident cardiac progenitor cell (CPC) activation and proliferation are crucial for endogenous cardiac regeneration and cardiac repair after myocardial infarction (MI). This study aims to explore the role and possible mechanisms of CB2 receptor activation in enhancing myocardial repair. Our results revealed that CB2 receptor agonist AM1241 can significantly increase CPCs by c-kit and Runx1 staining in ischemic myocardium as well as improve cardiomyocyte proliferation. AM1241 also decreased serum levels of MDA, TNF-α and IL-6 after MI. In addition, AM1241 can ameliorate left ventricular ejection fraction and fractional shortening, and reduce fibrosis. Moreover, AM1241 treatment markedly increased p-Akt and HO-1 expression, and promoted Nrf-2 nuclear translocation. However, PI3K inhibitor wortmannin eliminated these cardioprotective roles of AM1241. In conclusion, AM1241 could induce myocardial regeneration and improve cardiac function, which might be associated with PI3K/Akt/Nrf2 signaling pathway activation. Our findings may provide a promising strategy for cardiac endogenous regeneration after MI.

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Effects of cannabinoid receptor type 2 on endogenous myocardial regeneration by activating cardiac progenitor cells in mouse infarcted heart

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