title: Membrane estrogen receptor alpha is an important modulator of bone marrow C-Kit+ cells mediated cardiac repair after myocardial infarction.
abstract: 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 (ERα) is involved in adaptive mechanisms by supporting cardiomyocytes survival via post-infarct cardiac c-kit+ cells, we tested a novel hypothesis that membrane ERα (mERа) 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 mERа in post-infarct BM c-kit+ cells was found in day 3 post MI. In vitro co-culture system, mERа+ enhances the beneficial effects of BM c-kit+ cells by increasing their viability and reducing apoptosis. Post-infarct c-kit+ mERа+ cells population expresses predominant ERα 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+ mERа+ exerted significantly cardiac protection after MI. A potential important implication of this study is that the manipulation of BM c-kit+ stem cells with ERа-dependent fashion may be helpful in recovering functional performance after cardiac tissue injury.
authors.affiliation: Department of Cardiology, Yangpu Hospital, Tongji University School of Medicine Shanghai 200065, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Su
authors.affiliation: Department of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai 200127, China.
authors.forename: Wentian
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Renji-Med X Clinical Stem Cell Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai 200127, China.
authors.forename: Jianfang
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002470:Cell Survival; D018920:Coculture Techniques; D004195:Disease Models, Animal; D047628:Estrogen Receptor alpha / Q000096:biosynthesis*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D019089:Stem Cell Factor / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D011956:Receptors, Cell Surface; D019089:Stem Cell Factor
keywords: Acute myocardial infarction; cardiac repair; estrogen receptor alpha; stem cells