Membrane estrogen receptor alpha is an important modulator of bone marrow C-Kit( ) cells mediated cardiac repair after myocardial infarction

作者：Su, Feng; Zhang, Wentian; Liu, Jianfang^*

来源：International Journal of Clinical and Experimental Pathology, 2015, 8(5): 4284-U1760.

• Acute myocardial infarction
• stem cells
• estrogen receptor alpha
• cardiac repair

It has been validated that c-kit positive (c-kit( )) cells in infarcted myocardium are from bone marrow (BM). Given the recent study that in the heart, estrogen receptor alpha (ER alpha) is involved in adaptive mechanisms by supporting cardiomyocytes survival via post-infarct cardiac c-kit( ) cells, we tested a novel hypothesis that membrane ER alpha (mER.) supports survival of BM c-kit( ) cells and enhance protective paracrine function for cardiac repair. Our data showed that myocardial infarction (MI) leads to an increase in c-kit( ) first in bone marrow and then specifically within the infarcted myocardium. Also up-regulated mERa in post-infarct BM c-kit( ) cells was found in day 3 post MI. In vitro co-culture system, mERa( ) enhances the beneficial effects of BM c-kit( ) cells by increasing their viability and reducing apoptosis. Post-infarct c-kit( ) mERa( ) cells population expresses predominant ER alpha and holds self-renewal as well as cardiac differentiation potentials after MI. In vivo, BM c-kit( ) cells reduced infarct size, fibrosis and improved cardiac function. In conclusion, BM c-kit( ) mERa( ) exerted significantly cardiac protection after MI. A potential important implication of this study is that the manipulation of BM c-kit( ) stem cells with ERa-dependent fashion may be helpful in recovering functional performance after cardiac tissue injury.

• 出版日期2015
• 单位上海交通大学; 同济大学