Cardiac c-kit+AT2+ Cell Population is Increased in Response to Ischemic Injury and Supports Cardiomyocyte Performance§

Authors


  • Author contributions: W.A.-X. conception and design, provision of study material, collection and assembly of data, data analysis and interpretation, manuscript writing; C.C.: conception and design, provision of study material; E.K.: provision of study material, collection and assembly of data; A.G.: provision of study material, collection and assembly of data; S.S.: provision of study material, collection and assembly of data; J.D.: provision of study material, data analysis and interpretation; K.K.: data analysis and interpretation; M.S.: data analysis and interpretation; H.I.: provision of study material, data analysis and interpretation; T.U.: conception and design, data analysis and interpretation, administrative support, financial support, final approval of manuscript; J.L.: conception and design, provision of study material, collection and assembly of data, data analysis and interpretation, manuscript writing, financial support, final approval of manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLS EXPRESS July 9, 2009.

Abstract

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

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