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Cyclosporin A does not block exercise-induced cardiac hypertrophy
Tess Hainsey1, Anna Csiszar, Shuangdan Sun
1Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
Insights
Cyclosporin A (CsA) did not prevent exercise-induced cardiac hypertrophy in rats. However, CsA alone altered myocardial gene expression, suggesting a shift towards a pathological phenotype.
Area of Science:
- Cardiology
- Exercise Physiology
- Molecular Biology
Background:
- Cyclosporin A (CsA) inhibits pathological cardiac hypertrophy, implicating calcium-dependent pathways.
- The effect of CsA on exercise-induced cardiac hypertrophy, a physiological overload model, is not well understood.
Purpose of the Study:
- To investigate whether CsA alters exercise-induced cardiac hypertrophy in a rodent model.
Main Methods:
- Male rats received CsA or vehicle, followed by sedentary or swim training for one week.
- Cardiac hypertrophy markers, including ventricular weight and myosin heavy chain (MHC) expression, were analyzed.
Main Results:
- Swim training increased left ventricular weight and atrial natriuretic factor (ANF)-mRNA, but not alpha-myosin heavy chain (MHC).
- CsA treatment significantly increased beta-myosin heavy chain (MHC) expression at both mRNA and protein levels.
- CsA did not block exercise-induced cardiac hypertrophy but influenced myocardial phenotype.
Conclusions:
- Calcium-dependent pathways are not essential for early exercise-induced cardiac adaptations.
- CsA alone may induce a shift in MHC isoform expression towards a pathological phenotype.
- The impact of CsA-induced phenotype shifts on exercise capacity in transplant patients requires further investigation.
Unlabelled:
Cyclosporin A (CsA) has been shown to inhibit pathophysiological models of overload-induced cardiac hypertrophy, indicating a role for the calcium dependent signal pathways. It is unclear what impact CsA may have on the myocardial response to exercise, a physiological model of overload.
Purpose:
The purpose of the study was to determine whether CsA would alter exercise-induced cardiac hypertrophy.
Methods:
Thirty male rats were assigned to vehicle or CsA injection (15 mg.kg.d(-1)) and then assigned to sedentary or exercise training. Animals were swum for 60 min.d(-1) for 1 wk.
Results:
One week of swim training significantly increased plantaris cytochrome oxidase activity, as well as significantly increasing left ventricular (LV) weight and the left ventricular:body weight (LV/BW) ratio. Exercise did not alter right ventricular (RV) weight or the RV/BW ratio. RNA analysis found that exercise significantly increased atrial natriuretic factor (ANF)-mRNA levels but did not influence alpha-myosin heavy chain (MHC) expression. CsA treatment, but not exercise, was associated with a significant increase in betaMHC expression. Western blot analysis determined that betaMHC protein was also significantly increased in the CsA-treated animals.
Conclusion:
CsA did not block exercise-induced cardiac hypertrophy but did significantly influence the myocardial phenotype. The CsA-sensitive calcium dependent pathways, important for pathological forms of overload-induced hypertrophy, were not essential to the early adaptations to exercise and that a different mechanism or signal transduction pathway was engaged. The data also indicate that CsA alone may induce a shift in the MHC isoform expression toward that associated with a pathological phenotype. Whether this phenotype shift contributes to the lowered exercise capacity found in transplant patients remains to be determined.