Endothelial cell modulation of cardiomyocyte gene expression
Publisher DOI
PubMed ID
31442451
Abstract
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.
Date Issued
2019-10
Publication Type
Article
Subject(s)
Subjects
Angiopoietin-2
•
Cardiomyocytes
•
Co-culture
•
Endothelial cells
•
Endothelin-1
•
Fetal gene expression
Language(s)
en
Author(s)
Mohr, Franziska | |
Hecker, Markus | |
Wagner, Andreas H. |
Additional Credits
Journal
Endothelial cell modulation of cardiomyocyte gene expression
Publisher
Elsevier
ISSN
1090-2422
0014-4827
Access(Rights)
Unknown