
Systems Genetics Approach Identifies Gene Pathways and Adamts2 as Drivers of Isoproterenol-Induced Cardiac Hypertrophy and Cardiomyopathy in Mice.
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.
Duke Scholars
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Related Subject Headings
- Ventricular Remodeling
- Systems Biology
- Signal Transduction
- Myocytes, Cardiac
- Myocardium
- Mice, Inbred Strains
- Mice
- Isoproterenol
- Heart Ventricles
- Heart Failure
Citation

Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Ventricular Remodeling
- Systems Biology
- Signal Transduction
- Myocytes, Cardiac
- Myocardium
- Mice, Inbred Strains
- Mice
- Isoproterenol
- Heart Ventricles
- Heart Failure