| Title |
Gene expression analysis to identify mechanisms underlying heart failure susceptibility in mice and humans
|
|---|---|
| Published in |
Basic Research in Cardiology, December 2017
|
| DOI | 10.1007/s00395-017-0666-6 |
| Pubmed ID | |
| Authors |
Christoph Koentges, Mark E. Pepin, Carolyn Müsse, Katharina Pfeil, Sonia V. Viteri Alvarez, Natalie Hoppe, Michael M. Hoffmann, Katja E. Odening, Samuel Sossalla, Andreas Zirlik, Lutz Hein, Christoph Bode, Adam R. Wende, Heiko Bugger |
| 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. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 67% |
| Unknown | 1 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 44 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 44 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 8 | 18% |
| Researcher | 6 | 14% |
| Student > Bachelor | 5 | 11% |
| Student > Ph. D. Student | 3 | 7% |
| Student > Doctoral Student | 2 | 5% |
| Other | 8 | 18% |
| Unknown | 12 | 27% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 11 | 25% |
| Biochemistry, Genetics and Molecular Biology | 7 | 16% |
| Agricultural and Biological Sciences | 5 | 11% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 5% |
| Business, Management and Accounting | 1 | 2% |
| Other | 5 | 11% |
| Unknown | 13 | 30% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 July 2018.
All research outputs
#14,874,178
of 25,042,800 outputs
Outputs from Basic Research in Cardiology
#463
of 708 outputs
Outputs of similar age
#231,241
of 453,981 outputs
Outputs of similar age from Basic Research in Cardiology
#3
of 3 outputs
Altmetric has tracked 25,042,800 research outputs across all sources so far. This one is in the 40th percentile – i.e., 40% of other outputs scored the same or lower than it.
So far Altmetric has tracked 708 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.2. This one is in the 34th percentile – i.e., 34% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 453,981 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 3 others from the same source and published within six weeks on either side of this one.