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| Status |
Public on Jan 04, 2018 |
| Title |
Relaxin reverses inflammatory and immune signals in aged hearts |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background: ‘Healthy’ aging drives structural and functional changes in the heart including maladaptive electrical remodeling, fibrosis and inflammation, which lower the threshold for cardiovascular diseases such as heart failure (HF) and atrial fibrillation (AF). Despite mixed results in recent clinical trials, Relaxin-therapy for 2-days could reduce mortality by 37% at 180-days post-treatment, in patients with acute decompensated HF. Relaxin’s short life-span (hours) but long-lasting protective actions led us to test the hypothesis that relaxin acts at a genomic level to reverse maladaptive remodeling in aging and HF.
Methods and Results: Young (9-month) and aged (24-month), male and female F-344/Brown Norway rats were treated with relaxin (0.4 mg/kg/day) for 2-weeks delivered by subcutaneous osmotic mini-pumps or with sodium acetate (controls). The genomic effects of aging and relaxin were evaluated by extracting RNA from the left ventricles and analyzing genomic changes by RNA-sequencing, Ingenuity Pathway Analysis, MetaCore and tissue immunohistochemistry. We found that aging promotes a native inflammatory response with distinct sex-differences and relaxin suppresses transcription of multiple genes and signaling pathways associated with inflammation and HF in both genders. In addition, aging significantly increased macrophage infiltration in the ventricles and activation of the complement cascade, and relaxin reversed these age-related effects.
Conclusion: These data support the hypothesis that relaxin alters gene transcription and suppresses inflammatory pathways and genes associated with HF and aging. Relaxin’s suppression of inflammation and fibrosis supports its potential as a therapy for cardiovascular and inflammation-related diseases, such as HF, AF and diabetes.
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| Overall design |
There were 12 Males Samples (3/group) with 4 technical replicants and 16 Female Samples (4/group) with 4 techincal replicants.
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| Contributor(s) |
Martin B, Gabris-Weber B, Romero G, Chattophadhyay A, Salama G |
| Citation(s) |
29346407 |
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| Submission date |
Oct 31, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Brian Martin |
| E-mail(s) |
bmartin027@gmail.com
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| Organization name |
University of Pittsburgh
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| Department |
Bioengineering
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| Lab |
Salama
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| Street address |
3550 Terrace St
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| City |
Pittsburgh |
| State/province |
Pennsylvania |
| ZIP/Postal code |
15261 |
| Country |
USA |
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| Platforms (1) |
| GPL20084 |
Illumina NextSeq 500 (Rattus norvegicus) |
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| Samples (21)
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| GSM2836818 |
Female RLX treated Rat 1- 24 months old |
| GSM2836819 |
Female RLX treated Rat 2- 24 months old |
| GSM2836820 |
Female RLX treated Rat 4- 24 months old |
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| Relations |
| BioProject |
PRJNA416509 |
| SRA |
SRP123212 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE106377_Female_24_month_Control_and_RLX_treated.xlsx |
8.0 Mb |
(ftp)(http) |
XLSX |
| GSE106377_Female_24_month_and_9_month_Controls.xlsx |
8.1 Mb |
(ftp)(http) |
XLSX |
| GSE106377_Male_24_month_Control_and_RLX_treated.xlsx |
6.2 Mb |
(ftp)(http) |
XLSX |
| GSE106377_Male_24_month_and_9_month_Controls.xlsx |
6.2 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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