Open AccessCardiac c‐kit+AT2+ Cell Population is Increased in Response to Ischemic Injury and Supports Cardiomyocyte Performance
Author(s) -
AltarcheXifró Wassim,
Curato Caterina,
Kaschina Elena,
Grzesiak Aleksandra,
Slavic Svetlana,
Dong Jun,
Kappert Kai,
Steckelings Muscha,
Imboden Hans,
Unger Thomas,
Li Jun
Publication year - 2009
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.171
Subject(s) - biology , population , downregulation and upregulation , receptor , cardioprotection , angiotensin ii , medicine , microbiology and biotechnology , myocardial infarction , biochemistry , environmental health , gene
The expression pattern of angiotensin AT2 receptors with predominance during fetal life and upregulation under pathological conditions during tissue injury/repair process suggests that AT2 receptors may exert an important action in injury/repair adaptive mechanisms. Less is known about AT2 receptors in acute ischemia‐induced cardiac injury. We aimed here to elucidate the role of AT2 receptors after acute myocardial infarction. Double immunofluorescence staining showed that cardiac AT2 receptors were mainly detected in clusters of small c‐kit+ cells accumulating in peri‐infarct zone and c‐kit+AT2+ cells increased in response to acute cardiac injury. Further, we isolated cardiac c‐kit+AT2+ cell population by modified magnetic activated cell sorting and fluorescence activated cell sorting. These cardiac c‐kit+AT2+ cells, represented ∼0.19% of total cardiac cells in infarcted heart, were characterized by upregulated transcription factors implicated in cardiogenic differentiation (Gata‐4, Notch‐2, Nkx‐2.5) and genes required for self‐renewal (Tbx‐3, c‐Myc, Akt). When adult cardiomyocytes and cardiac c‐kit+AT2+ cells isolated from infarcted rat hearts were cocultured, AT2 receptor stimulation in vitro inhibited apoptosis of these cocultured cardiomyocytes. Moreover, in vivo AT2 receptor stimulation led to an increased c‐kit+AT2+ cell population in the infarcted myocardium and reduced apoptosis of cardiomyocytes in rats with acute myocardial infarction. These data suggest that cardiac c‐kit+AT2+ cell population exists and increases after acute ischemic injury. AT2 receptor activation supports performance of cardiomyocytes, thus contributing to cardioprotection via cardiac c‐kit+AT2+ cell population. STEM CELLS 2009;27:2488–2497