We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Gene expression analysis to identify mechanisms underlying heart failure susceptibility in mice and humans.
- Authors
Koentges, Christoph; Pepin, Mark E.; Müsse, Carolyn; Pfeil, Katharina; Alvarez, Sonia V. Viteri; Hoppe, Natalie; Hoffmann, Michael M.; Odening, Katja E.; Sossalla, Samuel; Zirlik, Andreas; Hein, Lutz; Bode, Christoph; Wende, Adam R.; Bugger, Heiko
- Abstract
Genetic factors are known to modulate cardiac susceptibility to ventricular hypertrophy and failure. To determine how strain infuences the transcriptional response to pressure overload-induced heart failure (HF) and which of these changes accurately refect the human disease, we analyzed the myocardial transcriptional profle of mouse strains with high (C57BL/6J) and low (129S1/SvImJ) susceptibility for HF development, which we compared to that of human failing hearts. Following transverse aortic constriction (TAC), C57BL/6J mice developed overt HF while 129S1/SvImJ did not. Despite a milder aortic constriction, impairment of ejection fraction and ventricular remodeling (dilation, fbrosis) was more pronounced in C57BL/6J mice. Similarly, changes in myocardial gene expression were more robust in C57BL/6J (461 genes) compared to 129S1/SvImJ mice (71 genes). When comparing these patterns to human dilated cardiomyopathy (1344 genes), C57BL/6J mice tightly grouped to human hearts. Overlay and bioinformatic analysis of the transcriptional profles of C57BL/6J mice and human failing hearts identifed six co-regulated genes (POSTN, CTGF, FN1, LOX, NOX4, TGFB2) with established link to HF development. Pathway enrichment analysis identifed angiotensin and IGF-1 signaling as most enriched putative upstream regulator and pathway, respectively, shared between TAC-induced HF in C57BL/6J mice and in human failing hearts. TAC-induced heart failure in C57BL/6J mice more closely refects the gene expression pattern of human dilated cardiomyopathy compared to 129S1/SvImJ mice. Unbiased as well as targeted gene expression and pathway analyses identifed periostin, angiotensin signaling, and IGF-1 signaling as potential causes of increased HF susceptibility in C57BL/6J mice and as potentially useful drug targets for HF treatment.
- Publication
Basic Research in Cardiology, 2018, Vol 113, Issue 1, p1
- ISSN
0300-8428
- Publication type
Article
- DOI
10.1007/s00395-017-0666-6