Macrophages mediate cardioprotective cellularpostconditioning in acute myocardial infarction (The Journal of Clinical Investigation, 2016,125(8):3147-62)

報告日期: 2016/11/22
報告時間: 4:00/4:50
報告學生: 林詠卿
講評老師: 劉秉彥
附件下載: 下載[1601-1473728287-1.pdf] 

Macrophages mediate cardioprotective cellular postconditioning in acute myocardial infarction

The Journal of Clinical Investigation, 2016,125(8):3147-62

Speaker: Yung-Ching Lin  

Commentator: Prof. Ping-Yen Liu

Date: 2016 / 11 / 22

Abstract

Acute myocardial infarction is one of the leading causes of morbidity and mortality worldwide. It causes myocardial ischemia then leads to recruit both pro-inflammatory (M1) and healing (M2) phenotype macrophages. Cardiosphere-derived cells (CDCs), a unique heart-derived cell type, has been demonstrated to be safe and effective in cardioprotection by intracoronary delivery in porcine and human chronic myocardial infarction1. However, the mechanism of CDCs is not clear. The authors subjected rats to 45 minutes of ischemia, followed by 20 minutes of reperfusion. CDCs (5x105 cells) or PBS as vehicle control were injected. CDC-treated rats showed smaller infarct size and better cardiac function comparing to control rats. The cardioprotective effect of CDCs was sustained for 2 weeks after ischemia/reperfusion (IR). But the benefit effects were not observed in delayed injection (infused 2 hours after IR). In cytokines protein arrays, they found the proteins associated with macrophage inactivation and responding to stimulation were elevated. This indicated that macrophages might be involved in the cardioprotective effect of CDCs. After systemic depletion of endogenous macrophages, the cardioprotection of CDCs was reduced. Cardiac macrophages isolated from CDC-treated rats have a distinct cytokine gene expression, protein marker expression, surface marker, and phagocytic capacity. Polarized macrophages (M1, M2, or MCDC) or vehicle control were infused into rats 20 minutes after IR, smaller infarct size was observed in CDC-treated rats. Authors revealed that macrophages as the key effectors in the cardioprotection of CDCs.

  1. Cellular postconditioning: allogeneic cardiosphere-derived cells reduce infarct size and attenuate microvascular obstruction when administered after reperfusion in pigs with acute myocardial infarction. Circ Heart Fail. (2015)