Cardiac c-kit+AT2+ cell population is increased in response to ischemic injury and supports cardiomyocyte performance

Altarche-Xifro, W.; Curato, C.; Kaschina, E.; Grzesiak, A.; Slavic, S.; Dong, J.; Kappert, K.; Steckelings, M.; Imboden, H.; Unger, T.; Li, J. (2009). Cardiac c-kit+AT2+ cell population is increased in response to ischemic injury and supports cardiomyocyte performance. Stem cells, 27(10), pp. 2488-97. Durham: AlphaMed Press 10.1002/stem.171

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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 approximately 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.

Item Type:	Journal Article (Original Article)
Division/Institute:	08 Faculty of Science > Department of Biology > Institute of Cell Biology
UniBE Contributor:	Imboden, Johann
ISSN:	1066-5099
Publisher:	AlphaMed Press
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 15:21
Last Modified:	05 Dec 2022 14:25
Publisher DOI:	10.1002/stem.171
Web of Science ID:	000271830200012
Additional Information:	peer-reviewed
URI:	https://boris.unibe.ch/id/eprint/36702 (FactScience: 205938)