Beneficial effects of exercise initiated before development of hypertrophic cardiomyopathy in genotype-positive mice.
Level 5 - mechanism / opinion, no new human data
Preclinical animal research
PubMed 37115627 · doi:10.1152/ajpheart.00701.2022
What was done
Genotype-positive Myh6 R403Q mice received either 6 weeks of high-intensity interval treadmill running or sedentary housing. Hypertrophic cardiomyopathy (HCM) phenotype was accelerated by administering cyclosporine A (CsA) starting at week 4. Cardiac imaging and exercise capacity tests were evaluated at weeks 0, 3, and 6. Following 6 weeks, hearts were evaluated for arrhythmia inducibility ex vivo, and left ventricles were harvested for histological fibrosis and molecular analyses of extracellular matrix (ECM) gene expression and intracellular signaling pathways.
What was found
The abstract reports no numeric values. Exercised HCM mice achieved greater running distance and speed and exhibited attenuated left atrial dilatation compared with sedentary controls. Histological cardiac fibrosis did not differ between exercised and sedentary HCM groups, despite exercised mice showing reduced expression of key ECM genes (collagen 1 and 3, fibronectin, and lysyl oxidase) alongside increased activation of Akt, GSK3b, and p38 signaling. Left ventricular function was not negatively affected by exercise.
Why it matters
The findings provide preclinical evidence that starting exercise training prior to overt HCM phenotype development does not induce cardiac dysfunction and may confer structural and molecular benefits.
Limits
The study was conducted in a chemically accelerated (CsA) mouse model, which may not directly mirror human genotype-positive disease progression. The abstract does not report the sample size (n), quantitative data, or confidence intervals. Long-term clinical endpoints and hard outcomes in humans were not evaluated.
Cited by
- supports Recent evidence indicates that patients with hypertrophic cardiomyopathy can safely train, and animal data suggests that exercise training at a young age may prevent the full expression of the disease.