Apelin prevents cardiac fibroblast activation and collagen production through inhibition of sphingosine kinase 1
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Summary
This summary is machine-generated.Apelin, a cardioprotective factor, inhibits cardiac fibroblast activation and collagen production by reducing sphingosine kinase 1 activity. This finding offers potential new therapies for heart failure by preventing fibrotic remodelling and improving ventricular function.
Area Of Science
- Cardiovascular Biology
- Fibrosis Research
- Molecular Cardiology
Background
- Cardiac fibroblast activation and myofibroblast differentiation drive cardiac fibrosis and heart failure.
- Apelin, an adipocyte-derived factor, has known cardioprotective effects, but its role in cardiac fibrosis is unexplored.
Purpose Of The Study
- To investigate the effects of apelin on cardiac fibroblast activation and myofibroblast differentiation.
- To elucidate the underlying mechanisms of apelin's action.
- To assess apelin's impact on cardiac fibrotic remodeling in vivo.
Main Methods
- In vitro studies using mouse cardiac fibroblasts treated with apelin and Transforming growth factor-β (TGF-β).
- Assessment of myofibroblast markers (α-smooth muscle actin) and collagen production.
- In vivo studies utilizing a mouse model of pressure overload (aortic banding) with apelin administration.
- Analysis of sphingosine kinase 1 (SphK1) activity and cardiac remodeling parameters.
Main Results
- Apelin inhibited TGF-β-induced α-smooth muscle actin expression and collagen production in cardiac fibroblasts.
- Apelin reduced spontaneous collagen production in fibroblasts from pressure-overloaded hearts.
- Apelin's antifibrotic effect was mediated by the inhibition of SphK1 activity.
- In vivo, apelin attenuated myocardial fibrosis, SphK1 activity, and α-SMA expression.
- Apelin administration post-aortic banding prevented cardiac remodeling, myocyte hypertrophy, fibrosis, and ventricular dysfunction.
Conclusions
- Apelin inhibits TGF-β-stimulated cardiac fibroblast activation via a SphK1-dependent pathway.
- Apelin administration during reactive fibrosis prevents myocardial structural remodeling and ventricular dysfunction.
- These findings suggest apelin as a potential therapeutic agent for heart failure associated with fibrotic remodeling.