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| Status |
Public on Jan 01, 2015 |
| Title |
The TIMP3/Apelin axis Regulates Atherosclerosis and Heart Metabolism leading to increased mortality in ApoE null Mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The role of TIMP3 in the context of cardiovascular remodeling is relatively unexplored when considering classical risk factors such as hypercholesterolemia, diabetes and hypertension. To learn more the role of TIMP3 in the progression of cardiovascular disease we combined genetics, metabolomics and in vivo phenotypical analysis using the hypercholesterolemic ApoE null mice to generate ApoE-/-Timp3-/- mice, the latter showing increased atherosclerosis, increased mortality and arrhythmias compared to ApoE-/- mice. We have previously described Timp3-/-mice in ( Fiorentino, L., et al., Regulation of TIMP3 in diabetic nephropathy: a role for microRNAs. Acta Diabetol, 2013) . To generate ApoE-/-Timp3-/- knockout animals we crossbred the 2 strains. Offsprings were then backcrossed into ApoE animals for 6 generations to generate a pure lineage. Collectively, metabolite profiles, gene and protein expression consistently suggested a role for TIMP3 to underlie a decreased activation of PPARα/AMPK to dampen fatty acids β-oxidation eventually leading to atherosclerotic plaque composition vulnerability and perturbation of heart metabolism. mRNA profiling in ApoE-/-Timp3-/- mice revealed a TIMP3 effect to regulate Apelin, which we found decreased in the circulation due to its specific downregulation at the myocardial level but not in other well known sites of expression such as the adipose tissue.
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| Overall design |
mRNA sequencing of the heart of ApoE-/-Timp3-/- mice vs ApoE-/- littermates controls.
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| Contributor(s) |
Stoehr R, Cavalera M, Carnevale D, Mavilio M, Menini S, Casagrande V, Rizza S, Cardellini M, Arisi I, Cattaneo A, Khokha R, Pugliese G, Menghini R, Mauriello A, Lembo G, Federici M |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Dec 20, 2013 |
| Last update date |
Mar 19, 2019 |
| Contact name |
Ivan Arisi |
| E-mail(s) |
i.arisi@ebri.it
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| Phone |
+39-06-49255230
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| Organization name |
European Brain Research Institute
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| Department |
Bioinformatics Facility
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| Street address |
viale Regina Elena 295
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| City |
Roma |
| ZIP/Postal code |
00161 |
| Country |
Italy |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA232389 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE53548_RAW.tar |
56.8 Mb |
(http)(custom) |
TAR (of GTF) |
| Raw data not provided for this record |
| Processed data provided as supplementary file |
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