title: Original Research: Atorvastatin prevents rat cardiomyocyte hypertrophy induced by parathyroid hormone 1-34 associated with the Ras-ERK signaling.
abstract: 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, 4 × 10(-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 µm, 1622 cpm/well, 84.34 pg, 7.13 ng/L and 20.04 µg/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 µm, 750 cpm/well, 49.08 pg, 3.12 ng/L and 9.35 µg/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.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China zouschbo@163.com.
authors.forename: Chunbo
authors.initials: C
authors.lastname: Zou
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Chengyuan
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Rujuan
authors.initials: R
authors.lastname: Xie
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Manshu
authors.initials: M
authors.lastname: Sui
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Suhong
authors.initials: S
authors.lastname: Mu
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Shilei
authors.initials: S
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000069059:Atorvastatin / Q000627:therapeutic use*; D015153:Blotting, Western; D002312:Cardiomyopathy, Hypertrophic / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D048429:Cell Size / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010281:Parathyroid Hormone; D000069059:Atorvastatin
keywords: 3H-leucine incorporation; The hypertrophic responses of cardiomyocytes; atorvastatin; atrial natriuretic peptide; brain natriuretic peptide; mevalonic acid