| First Author | Edling CE | Year | 2019 |
| Journal | Biosci Rep | Volume | 39 |
| Issue | 12 | PubMed ID | 31778152 |
| Mgi Jnum | J:298237 | Mgi Id | MGI:6472151 |
| Doi | 10.1042/BSR20190403 | Citation | Edling CE, et al. (2019) Molecular basis of arrhythmic substrate in ageing murine peroxisome proliferator-activated receptor gamma co-activator deficient hearts modelling mitochondrial dysfunction. Biosci Rep 39(12) |
| abstractText | INTRODUCTION: Ageing and chronic metabolic disorders are associated with mitochondrial dysfunction and cardiac pro-arrhythmic phenotypes which were recently attributed to slowed atrial and ventricular action potential (AP) conduction in peroxisome proliferator-activated receptor gamma co-activator deficient (Pgc-1beta-/-) mice. METHODS: We compared expression levels of voltage-gated Na+ channel (NaV1.5) and gap junction channels, Connexins 40 and 43 (Cx40 and Cx43) in the hearts of young and old, and wild-type (WT) and Pgc-1beta-/- mice. This employed Western blotting (WB) for NaV1.5, Cx40 and Cx43 in atrial/ventricular tissue lysates, and immunofluorescence (IF) from Cx43 was explored in tissue sections. Results were analysed using two-way analysis of variance (ANOVA) for independent/interacting effects of age and genotype. RESULTS: In atria, increased age and Pgc-1beta-/- genotype each independently decreased both Cx40 and Cx43 expression without interacting effects. In IF experiments, both age and Pgc-1beta deletion independently reduced Cx43 expression. In ventricles, age and genotype exerted interacting effects in WB studies of NaV1.5 expression. Young Pgc-1beta-/- then showed greater NaV1.5 expression than young WT ventricles. However, neither age nor Pgc-1beta deletion affected Cx43 expression, independently or through interacting effects in both WB and IF studies. CONCLUSION: Similar pro-arrhythmic atrial/ventricular phenotypes arise in aged/Pgc-1beta-/- from differing contributions of altered protein expression and functional effects that may arise from multiple acute mechanisms. |
