Back to Search
Start Over
Systems Genetics Approach Identifies Gene Pathways and Adamts2 as Drivers of Isoproterenol-Induced Cardiac Hypertrophy and Cardiomyopathy in Mice.
- Source :
-
Cell systems [Cell Syst] 2017 Jan 25; Vol. 4 (1), pp. 121-128.e4. Date of Electronic Publication: 2016 Nov 17. - Publication Year :
- 2017
-
Abstract
- We previously reported a genetic analysis of heart failure traits in a population of inbred mouse strains treated with isoproterenol to mimic catecholamine-driven cardiac hypertrophy. Here, we apply a co-expression network algorithm, wMICA, to perform a systems-level analysis of left ventricular transcriptomes from these mice. We describe the features of the overall network but focus on a module identified in treated hearts that is strongly related to cardiac hypertrophy and pathological remodeling. Using the causal modeling algorithm NEO, we identified the gene Adamts2 as a putative regulator of this module and validated the predictive value of NEO using small interfering RNA-mediated knockdown in neonatal rat ventricular myocytes. Adamts2 silencing regulated the expression of the genes residing within the module and impaired isoproterenol-induced cellular hypertrophy. Our results provide a view of higher order interactions in heart failure with potential for diagnostic and therapeutic insights.<br /> (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- ADAMTS Proteins physiology
Animals
Cardiomegaly chemically induced
Cardiomyopathies genetics
Cardiomyopathies metabolism
Cardiomyopathies physiopathology
Cardiotonic Agents adverse effects
Catecholamines adverse effects
Gene Expression Regulation drug effects
Gene Regulatory Networks genetics
Heart Failure genetics
Heart Ventricles metabolism
Isoproterenol pharmacology
Mice
Mice, Inbred Strains genetics
Myocardium metabolism
Myocytes, Cardiac metabolism
Signal Transduction drug effects
Ventricular Remodeling genetics
ADAMTS Proteins genetics
Cardiomegaly genetics
Systems Biology methods
Subjects
Details
- Language :
- English
- ISSN :
- 2405-4712
- Volume :
- 4
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cell systems
- Publication Type :
- Academic Journal
- Accession number :
- 27866946
- Full Text :
- https://doi.org/10.1016/j.cels.2016.10.016