Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Koentges, C; Pepin, ME; Müsse, C; Pfeil, K; Alvarez, SVV; Hoppe, N; Hoffmann, MM; Odening, KE; Sossalla, S; Zirlik, A; Hein, L; Bode, C; Wende, AR; Bugger, H.
Gene expression analysis to identify mechanisms underlying heart failure susceptibility in mice and humans.
Basic Res Cardiol. 2018; 113(1):8-8
Doi: 10.1007/s00395-017-0666-6
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- Führende Autor*innen der Med Uni Graz
- Bugger Heiko Matthias
- Co-Autor*innen der Med Uni Graz
- Pfeil Katharina
- Zirlik Andreas
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- Abstract:
- Genetic factors are known to modulate cardiac susceptibility to ventricular hypertrophy and failure. To determine how strain influences the transcriptional response to pressure overload-induced heart failure (HF) and which of these changes accurately reflect the human disease, we analyzed the myocardial transcriptional profile 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, fibrosis) 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 profiles of C57BL/6J mice and human failing hearts identified six co-regulated genes (POSTN, CTGF, FN1, LOX, NOX4, TGFB2) with established link to HF development. Pathway enrichment analysis identified 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 reflects the gene expression pattern of human dilated cardiomyopathy compared to 129S1/SvImJ mice. Unbiased as well as targeted gene expression and pathway analyses identified 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cardiomyopathy, Dilated - complications
- Cardiomyopathy, Dilated - genetics
- Cardiomyopathy, Dilated - physiopathology
- Case-Control Studies -
- Disease Models, Animal -
- Disease Progression -
- Gene Expression Profiling - methods
- Gene Expression Regulation -
- Gene Regulatory Networks -
- Genetic Predisposition to Disease -
- Heart Failure - genetics
- Heart Failure - physiopathology
- Hypertrophy, Left Ventricular - complications
- Hypertrophy, Left Ventricular - genetics
- Hypertrophy, Left Ventricular - physiopathology
- Male -
- Mice, 129 Strain -
- Mice, Inbred C57BL -
- Phenotype -
- Species Specificity -
- Transcriptome -
- Ventricular Function, Left - genetics
- Ventricular Remodeling - genetics
- Find related publications in this database (Keywords)
- Heart failure
- Transverse aortic constriction
- Gene expression
- Genetic background
- Cardiac function