Universität zu Köln

Argenziano, Mariana A., Doss, Michael Xavier, Tabler, Megan, Sachinidis, Agapios and Antzelevitch, Charles ORCID: 0000-0001-7349-1582 (2019). Transcriptional changes associated with advancing stages of heart failure underlie atrial and ventricular arrhythmogenesis. PLoS One, 14 (5). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Background Heart failure (HF) is a leading cause of mortality and is associated with cardiac remodeling. Vulnerability to atrial fibrillation (AF) has been shown to be greater in the early stages of HF, whereas ventricular tachycardia/fibrillation develop during late stages. Here, we explore changes in gene expression that underlie the differential development of fibrosis and structural alterations that predispose to atrial and ventricular arrhythmias. Objective To study transcriptomic changes associated with the development of cardiac arrhythmias in early and late stages of heart failure. Methods Dogs were tachy-paced from right ventricle (RV) for 2-3 or 5-6 weeks (early and late HF). We performed transcriptomic analysis of right atria (RA) and RV isolated from control dogs and those in early and late HF. Transcripts with mean relative log2-fold change >= 2 were included in the differential analysis with significance threshold adjusted to p<0.05. Results Early HF remodeling was more prominent in RA with enrichment of extracellular matrix, circulatory system, wound healing and immune response pathways; many of these processes were not present in RA in late HF. RV showed no signs of remodeling in early HF but enrichment of extracellular matrix and wound healing in late HF. Conclusion Our transcriptomic data indicate significant fibrosis-associated transcriptional changes in RA in early HF and in RV in late HF, with strong atrial predominance. These alterations in gene expression are consistent with the development of arrhythmogenesis in atria in early but not late HF and in the ventricle in late but not early HF.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Argenziano, Mariana A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Doss, Michael Xavier UNSPECIFIED UNSPECIFIED UNSPECIFIED Tabler, Megan UNSPECIFIED UNSPECIFIED UNSPECIFIED Sachinidis, Agapios UNSPECIFIED UNSPECIFIED UNSPECIFIED Antzelevitch, Charles UNSPECIFIED orcid.org/0000-0001-7349-1582 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-148292
DOI:	10.1371/journal.pone.0216928
Journal or Publication Title:	PLoS One
Volume:	14
Number:	5
Date:	2019
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FIBRILLATION; DOGS; UPDATE; MODEL; KEGG Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14829