Original Research: Atorvastatin prevents rat cardiomyocyte hypertrophy induced by parathyroid hormone 1-34 associated with the Ras-ERK signaling

摘要

We investigated the effects of atorvastatin (Ator) on cardiomyocyte hypertrophy (CMH) induced by rat parathyroid hormone 1-34 (PTH1-34) and Ras-extracellular signal regulated protein kinases 1/2 (ERK1/2) signaling. Rat cardiomyocytes were randomly divided into seven groups: normal controls (NC), PTH1-34 (10(-7)mol/L), Ator (10(-5)mol/L), farnesyl transferase inhibitors-276 (FTI-276, 4x10(-5)mol/L), PTH1-34+Ator, PTH1-34+FTI-276 and PTH1-34+Ator+mevalonic acid (MVA, 10(-4)mol/L). After treatment, the hypertrophic responses of cardiomyocytes were assessed by measuring cell diameter, detecting protein synthesis, and single-cell protein content. The concentrations of hypertrophic markers such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured by ELISA. Protein expressions of ERK1/2, p-ERK1/2 and Ras were detected by western blotting. The results showed that compared with the PTH1-34 group, cellular diameter, 3H-leucine incorporation, single-cell protein content, ANP and BNP concentration decreased by 12.07 mu m, 1622cpm/well, 84.34 pg, 7.13ng/L and 20.04 mu g/L, respectively, and the expressions of Ras and p-ERK1/2 were downregulated in PTH1-34+Ator group (P<0.05). Compared to the PTH1-34+Ator group, the corresponding hypertrophic responses and hypertrophic markers increased by 4.95 mu m, 750cpm/well, 49.08 pg, 3.12ng/L and 9.35 mu g/L, respectively, and the expressions of Ras and p-ERK1/2 were upregulated in the PTH1-34+Ator+MVA group (P<0.05). In conclusion, Ator prevents neonatal rat CMH induced by PTH1-34 and Ras-ERK signaling may be involved in this process.