eprintid: 25692
rev_number: 13
eprint_status: archive
userid: 4136
dir: disk0/00/02/56/92
datestamp: 2019-01-21 07:18:27
lastmod: 2019-02-19 17:41:24
status_changed: 2019-01-21 07:18:27
type: doctoralThesis
metadata_visibility: show
creators_name: Jiang, Fan
title: Endothelial cell modulation of cardiomyocyte gene expression
subjects: 610
divisions: 53200
adv_faculty: af-05
cterms_swd: Cardiac Hypertrophy
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 mRNA expression in cardiomyocytes and subsequent ANP release were significantly upregulated when co-cultured with endothelial cells or exposed to endothelial cell-conditioned medium. Endothelin-1 (ET-1) activation of endothelial cells remarkably enhanced their paracrine effects on cardiomyocyte gene expression in our study, suggesting for the first time that ET-1 stimulation of endothelial cells affects expression of fetal genes such as ANP and BNP in adult cardiomyocytes through paracrine signalling. Combined with previous results indicating a crucial role for ANP and BNP in cardiac homeostasis, our finding provide further evidence that paracrine signalling by cardiac microvascular endothelial cells modulates cardiomyocyte function. Exposure of HL-1 cells to authentic Angiopoietin-2 (Ang2) caused a concentration-dependent decrease in ANP expression while ET-1-induced ANP expression was augmented by low concentrations of Ang2 (1 ng/ml) but inhibited by high concentrations of Ang2 (10 ng/ml). Mass spectrometry analysis of EC-conditioned medium revealed qualitative differences in the release of proteins from endothelial cells with and without ET-1 stimulation. Gene ontology annotation of the detected proteins points towards a role for exosomes and proteins involved in RNA folding in endothelial cell-cardiomyocyte crosstalk.
date: 2019
id_scheme: DOI
id_number: 10.11588/heidok.00025692
ppn_swb: 1655138073
own_urn: urn:nbn:de:bsz:16-heidok-256928
date_accepted: 2018-11-23
advisor: HASH(0x564e1c3459d0)
language: eng
bibsort: JIANGFANENDOTHELIA2019
full_text_status: public
citation:   Jiang, Fan  (2019) Endothelial cell modulation of cardiomyocyte gene expression.  [Dissertation]     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/25692/1/Thesis-Fan.pdf