| First Author | Rau CD | Year | 2017 |
| Journal | Cell Syst | Volume | 4 |
| Issue | 1 | Pages | 121-128.e4 |
| PubMed ID | 27866946 | Mgi Jnum | J:351957 |
| Mgi Id | MGI:7703832 | Doi | 10.1016/j.cels.2016.10.016 |
| Citation | Rau CD, et al. (2017) Systems Genetics Approach Identifies Gene Pathways and Adamts2 as Drivers of Isoproterenol-Induced Cardiac Hypertrophy and Cardiomyopathy in Mice. Cell Syst 4(1):121-128.e4 |
| abstractText | 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. |
