Endothelial cell modulation of cardiomyocyte gene expression
The anatomic arrangement of microvascular endothelial cells and cardiomyocytes in vivo enables close interactions among these cells. In our in vitro co-culture system, ANP and BNP expression in the mouse atrial cardiomyocyte cell line HL-1 and subsequent ANP release were significantly upregulated wh...
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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
20 August 2019
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| In: |
Experimental cell research
Year: 2019, Volume: 383, Issue: 2 |
| ISSN: | 1090-2422 |
| DOI: | 10.1016/j.yexcr.2019.111565 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1016/j.yexcr.2019.111565 Verlag: http://www.sciencedirect.com/science/article/pii/S0014482719304173 |
| Author Notes: | Fan Jiang, Franziska Mohr, Nina D. Ullrich, Markus Hecker, Andreas H. Wagner |
| Summary: | The anatomic arrangement of microvascular endothelial cells and cardiomyocytes in vivo enables close interactions among these cells. In our in vitro co-culture system, ANP and BNP expression in the mouse atrial cardiomyocyte cell line HL-1 and subsequent ANP release were significantly upregulated when co-cultured with mouse cardiac microvascular endothelial cells or exposed to endothelial cell-conditioned medium. Endothelin-1 (ET-1) activation of endothelial cells remarkably enhanced their paracrine effect on cardiomyocyte gene expression, suggesting that ET-1 stimulation of endothelial cells affects expression of fetal genes such as ANP and BNP in adult cardiomyocytes through paracrine signalling. Exposure of HL-1cells and murine induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to authentic angiopoietin-2 (Ang2) caused a concentration-dependent decrease in ANP expression while ET-1-induced ANP expression was augmented by low but inhibited by high concentrations of Ang2. FK506-mediated inhibition of the calcineurin-NFAT pathway in the HL-1cells selectively inhibited the stimulatory effect of the conditioned medium derived from ET-1-pre-stimulated endothelial cells on cardiomyocyte fetal gene expression. Combined with previous results indicating a crucial role for ANP and BNP in cardiac homeostasis, our findings provide further evidence that paracrine signalling by cardiac microvascular endothelial cells modulates cardiomyocyte function. |
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| Item Description: | Gesehen am 24.10.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1090-2422 |
| DOI: | 10.1016/j.yexcr.2019.111565 |