Effects Of Calcineurin Signaling Pathway On Cardiomyocytes Hypertrophy Induced By Prostaglandin F2a In Rats

Objective: In the early stage, cardiac hypertrophy is a compensatory mechanism of the heart to improves cardiac pump function to maintain cardiac output for overload of heart under various pathological situations, including hypertension , vascular diseases , coronary heart diseases, the myocardiopathy and the heart valve diseases, however, sustained cardiac hypertrophy is rather a maladaptive process, ultimately leading to heart failure ,arrhythmias and sudden death. The Prostaglandin F2a (PGF2α) is discovered possibility causing cardiac hypertrophy, but the mechanism is not very clear. More recently, the Ca2 +/ CaM-CaN is considered to play a very important role in hypertrophy of cardiamyocytes or skeletal muscle cells. The present study was under taken to observe the effects of Ca2 +/CaM dependent CaN signaling pathway on cardiomyocytes hypertrophy induced by Prostaglandin F2a (PGF2a) in rats.Methods: Cardiomyocytes of neonatal Wistar rats were cultured with PGF2a in various concentrations (10.0μmol/ L, 1.0μmol/ L,0.1μmol/ L,0.01μmol/ L,0.001μmol/ L), cardiomyocyte hypertrophy was evaluated by measuring cell area and protein content. The calcineurin inhibitor Cyclosporine A (CsA) was used to prevented cardiac hypertrophy induced by 0.1μmol/ L PGF2a. Using Fura 2/ AM as a fluorescent indicator, the intracellular free calcium concentration ([Ca2 +] i) was measured. CaN-αprotein was assayed by Western-blot.Results: PGF2a significantly increased the protein content and cardiomyocyte area in four concentrations,include10.0μmol/ L,1.0μmol/ L,0.1μmol/ L,0.01μmol/ L PGF2a ( P < 0. 05),except the 0.001μmol/ L ( P >0. 05). and the protein content and cardiomyocyte area were increased most by 0.1μmol/ L PGF2a ,by 67.78±11.19%and 68.94±1.52%, respectively, which was abolished partly by CsA. [Ca2 +] i was elevated markedly in cardiomyocytes by 0.1μmol/ L PGF2a, as well as CaN-αprotein expression. Conclusion: Cardiomyocyte hypertrophy induced by PGF2a may be mediated through Ca2 +/CaM-CaN signaling pathway in rats.