| First Author | Lasheras J | Year | 2021 |
| Journal | Int J Mol Sci | Volume | 22 |
| Issue | 15 | PubMed ID | 34360813 |
| Mgi Jnum | J:310470 | Mgi Id | MGI:6762272 |
| Doi | 10.3390/ijms22158047 | Citation | Lasheras J, et al. (2021) Cardiac-Specific Overexpression of ERRgamma in Mice Induces Severe Heart Dysfunction and Early Lethality. Int J Mol Sci 22(15) |
| abstractText | Proper cardiac function depends on the coordinated expression of multiple gene networks related to fuel utilization and mitochondrial ATP production, heart contraction, and ion transport. Key transcriptional regulators that regulate these gene networks have been identified. Among them, estrogen-related receptors (ERRs) have emerged as crucial modulators of cardiac function by regulating cellular metabolism and contraction machinery. Consistent with this role, lack of ERRalpha or ERRgamma results in cardiac derangements that lead to functional maladaptation in response to increased workload. Interestingly, metabolic inflexibility associated with diabetic cardiomyopathy has been recently associated with increased mitochondrial fatty acid oxidation and expression of ERRgamma, suggesting that sustained expression of this nuclear receptor could result in a cardiac pathogenic outcome. Here, we describe the generation of mice with cardiac-specific overexpression of ERRgamma, which die at young ages due to heart failure. ERRgamma transgenic mice show signs of dilated cardiomyopathy associated with cardiomyocyte hypertrophy, increased cell death, and fibrosis. Our results suggest that ERRgamma could play a role in mediating cardiac pathogenic responses. |
