Endothelial cell modulation of cardiomyocyte gene expression

• Published in: Experimental cell research 2019-10, Vol.383 (2), p.111565-111565, Article 111565
• Main Authors: Jiang, Fan, Mohr, Franziska, Ullrich, Nina D., Hecker, Markus, Wagner, Andreas H.
• Format: Article
• Language: English
• Subjects: Angiopoietin-2; Cardiomyocytes; Co-culture; Endothelial cells; Endothelin-1; Fetal gene expression
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2019.111565

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-1 cells 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-1 cells 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. [Display omitted] •ET-1 enhanced paracrine effects of ECs on cardiomyocyte re-expression of the fetal gene program.•Ang2 affected ET-1-induced cardiomyocyte ANP expression and release in a dose-dependent manner.•Calcineurin-NFAT pathway plays a role in paracrine control of ANP expression in cardiomyocytes.