Ahmad, Shiraz

Chadda, Karan R

Edling, Charlotte E

Fazmin, Ibrahim T

Huang, Christopher

Jeevaratnam, Kamalan

Saadeh, Khalil

Valli, Haseeb

English

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 γ co-activator deficient (Pgc-1β-/-) 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-1β-/- 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-1β-/- genotype each independently decreased both Cx40 and Cx43 expression without interacting effects. In IF experiments, both age and Pgc-1β deletion independently reduced Cx43 expression. In ventricles, age and genotype exerted interacting effects in WB studies of NaV1.5 expression. Young Pgc-1β-/- then showed greater NaV1.5 expression than young WT ventricles. However, neither age nor Pgc-1β 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-1β-/- from differing contributions of altered protein expression and functional effects that may arise from multiple acute mechanisms

Huang, Christopher L-H

Apollo (Cambridge)

Molecular basis of arrhythmic substrate in ageing murine peroxisome proliferator-activated receptor γ co-activator deficient hearts modelling mitochondrial dysfunction.

https://www.repository.cam.ac.uk/bitstream/1810/300633/1/Molecular%20basis%20of%20arrhythmic%20substrate%20in%20ageing%20murine%20peroxisome%20proliferator-activated%20receptor%20%ce%b3%20co-activator%20deficient.pdf

Molecular basis of arrhythmic substrate in ageing murine peroxisome proliferator-activated receptor γ co-activator deficient hearts modelling mitochondrial dysfunction.

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Apollo (Cambridge)