Autor: |
Andreassen, K, Rixon, C, Hauge-Iversen, IM, Sjaastad, I, Christensen, G, Edvardsen, T, Haugaa, KH, Lunde, IG, Stokke, MK |
Předmět: |
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Zdroj: |
Cardiovascular Research; 2022 Supplement, Vol. 118, p1-1, 1p |
Abstrakt: |
Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): South-Eastern Norway Regional Health Authority (HSØ) KG Jebsen Cardiac Research Center Background The effects of exercise training prior to manifestation of phenotype in hypertrophic cardiomyopathy (HCM) are unknown. In mice carrying the HCM-pathogenic α-MHC R403Q/+ (R403Q) genetic variant, accelerated progression of the HCM phenotype is induced by cyclosporine A (CsA). We used this model to determine if exercise training initiated before phenotype development could limit disease severity. Methods R403Q mice were allocated to treadmill exercise training (N=23) or sedentary behavior (N=23) for 6 weeks. For the last three weeks of the 6-week period, all mice received CsA to induce the HCM phenotype. Cardiac imaging (echocardiography or MRI) and exercise testing were performed at the 0, 3 and 6-week time points. After the 6-week exercise protocol, left ventricles were harvested for molecular analyses. Results After 6 weeks, exercise trained mice ran 2-fold further during testing than sedentary mice (p<0.0001), and 2-fold further than at baseline (p<0.0001). There was no difference in VO2 max between groups. Cardiac imaging did not reveal differences in hypertrophy between exercised and sedentary HCM mice. However, we observed a reduction in cardiac expression of key fibrosis-related genes in the exercise group, i.e. Col1a2 to 49 % (p=0.03), Col1a1 to 50 % (p=0.03), Col3a1 to 46 % (p=0.02), Fn1 to 49 % (p=0.01) and Lox to 58 % (p=0.05) of levels in the sedentary group. HPLC did not reveal differences in collagen protein. Conclusion Exercise training initiated prior to manifestation of the HCM phenotype in mice results in lowered production of key fibrosis-related genes, including structural collagens. Further analysis is needed to determine the functional consequences of these beneficial changes in gene expression. Open in new tab Download slide Experimental protocol Open in new tab Download slide Fibrotic gene expression [ABSTRACT FROM AUTHOR] |
Databáze: |
Complementary Index |
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