First Author | Andreassen K | Year | 2023 |
Journal | Am J Physiol Heart Circ Physiol | Volume | 324 |
Issue | 6 | Pages | H881-H892 |
PubMed ID | 37115627 | Mgi Jnum | J:335533 |
Mgi Id | MGI:7471286 | Doi | 10.1152/ajpheart.00701.2022 |
Citation | Andreassen K, et al. (2023) Beneficial effects of exercise initiated prior to development of hypertrophic cardiomyopathy in genotype positive mice. Am J Physiol Heart Circ Physiol |
abstractText | The effect of exercise on disease development in hypertrophic cardiomyopathy (HCM) genotype positive individuals is unresolved. Our objective was to test the effect of exercise training initiated prior to phenotype development on cardiac fibrosis, morphology, and function in a mouse model of HCM. Genotype positive Myh6 R403Q mice exposed to cyclosporine A (CsA) for induction of HCM (HCM mice) were allocated to high intensity interval treadmill running or sedentary behavior for 6 weeks. CsA was initiated from week 4 of the protocol. Cardiac imaging and exercise testing were performed at weeks 0, 3, and 6. After protocol completion, arrhythmia provocation was performed in isolated hearts, and left ventricles (LVs) were harvested for molecular biology and histology. Exercised HCM mice ran farther and faster and exhibited attenuated left atrial (LA) dilatation compared to sedentary mice. Exercised HCM mice had no difference in fibrosis compared to sedentary HCM mice despite lower expression of key ECM genes collagen 1 and 3, fibronectin, and lysyl oxidase, accompanied by increased activation of Akt, GSK3b and p38. Exercise did not have negative effects on LV function in HCM mice. Our findings indicate mild beneficial effects of exercise initiated prior to HCM phenotype development, specifically lower ECM gene expression and LA dilatation, and importantly, no detrimental effects. |