Endurance Exercise Accelerates Pathology With Gene Mutation
(HealthDay News) — Endurance exercise seems to accelerate arrhythmogenic ventricular cardiomyopathy (AVC) pathogenesis in transgenic mice with the desmoplakin R2834H mutation (Tg-DSPR2834H), according to an experimental study published online November 6 in the American Journal of Physiology: Heart and Circulatory Physiology.
Ruben Martherus, PhD, from the Cincinnati Children's Hospital Medical Center, and colleagues examined how chronic endurance exercise contributes to DSP mutation-induced AVC pathogenesis. For 12 weeks, the authors exposed transgenic mice with overexpression of wild type DSP (Tg-DSPWT) or Tg-DSPR2834H, as well as control non-transgenic (NTg) littermates, to sedentary conditions or a daily running regimen.
The researchers found that 4–week old mice from all groups displayed normal cardiac function at baseline. All mice retained normal cardiac function and left ventricular morphology when subjected to exercise; Tg-DSPR2834H mutants, but not NTg and Tg-DSPWT, displayed right ventricular (RV) dilation and wall thinning. Focal fat infiltrations in RV and cytoplasmic aggregations consisting of desmoplakin, plakoglobin, and connexin43 were seen in Tg-DSPR2834H hearts. These aggregates coincided with disruption of the intercalated disks, intermediate filaments, and microtubules. After exercise Tg-DSPR2834H mice showed decrease of nuclear GSK3-β and AKT1 levels, with reduced p-GSK3-βSer9, p-AKT1Ser473, p-AKT1Ser308, and loss of nuclear JUP. In contrast, in response to exercise, Tg-DSPWT showed upregulation of p-AKT1Ser473, p-AKT1Ser308, and p-GSK3-βSer9.
"Our study suggests a potential mechanism-based approach to exercise management in patients with AVC," the authors write.