Caffeine induces cardiomyocyte hypertrophy via p300 and CaMKII pathways

•Found the appropriate concentration and duration of caffeine-induced hypertrophy.•CaMKII and p300 play the key roles in caffeine-induced cardiomyocyte hypertrophy.•Calcium transient amplitude is the key marker of cardiomyocyte hypertrophy.

Caffeine is commonly utilized to trigger intracellular calcium in cardiomyocyte. It is well accepted that caffeine could induce cardiac arrhythmia, but it is not clear with regard of its impacts on the cardiac function. This article presents a recent study concerning the effects of caffeine on the cardiomyocyte hypertrophy and the associated signal pathway. The experimental results showed that the total protein contents, the surface area of cardiomyocyte and β-myosin heavy chain (β-MHC) expression increased in ventricular myocytes of neonatal Sprague–Dawley (SD) rats after 24 h caffeine incubation. It is also observed that the basal intracellular calcium (Ca2+) level has increased, while the amplitude of Ca2+ oscillation and Ca2+ content have decreased in sarcoplasmic reticulum (SR). The caffeine-induced myocyte enhancer factor-2 (MEF2) expression and hypertrophy can be completely abolished by the inhibition of cardiac ryanodine receptor (RyR2), as well as KN93 and curcumin treatments. Meanwhile, the amplitude of Ca2+ oscillation and the Ca2+ content of SR in the completely-inhibited group have reached the physiological level. These results suggest that the caffeine-induced cardiomyocyte hypertrophy established the connection between Ca2+ release from SR and cytosol that activates CaMKII and p300, which in turn enhances the expression of MEF2 that promotes cardiomyocyte hypertrophy.

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