[Atorvastatin attenuates parathyroid hormone 1-34 induced cardiomyocytes hypertrophy through downregulating K-Ras-ERK1/2 pathway].
OBJECTIVE
To investigate the effects of atorvastatin on parathyroid hormone 1-34 (PTH1-34) induced neonatal rat cardiomyocytes hypertrophy and on the expression changes of small GTP-binding protein (K-Ras) and extracellular signal regulated protein kinases 1/2 (ERK1/2).


METHODS
Neonatal rat cardiomyocytes hypertrophy was established with 10(-7) mol/L rPTH1-34 in the presence or absence of 10(-5) mol/L atorvastatin or 10(-4) mol/L mevalonic acid (MVA). Cardiomyocyte diameter was measured by Motic Images Advanced 3.0 software, the synthetic rate of protein in cardiomyocytes was determined by (3)H-leucine incorporation and single-cell protein content was measured by BCA. The concentration of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were determined by ELISA. Protein expression of ERK1/2, p-ERK1/2 and K-Ras was detected by Western blot.


RESULTS
Compared to PTH1-34 group, cellular diameter was decreased 12.07 µm, (3)H-leucine incorporation decreased 1622 cpm/well and single-cell protein content decreased 84.34 pg, ANP or BNP concentration reduced 7.13 µg/L or 20.04 µg/L, protein expression of K-Ras, ERK1/2 or p-ERK1/2 downregulated 0.81, 0.19 and 1.44 fold, respectively, in PTH1-34 plus atrovastatin co-treated cardiomyocytes (all P < 0.05). Compared to PTH1-34 plus atrovastatin co-treated group, cardiomyocyte diameter increased 4.95 µm, (3)H-leucine incorporation increased 750 cpm/well and single-cell protein content increased 49.08 pg, ANP or BNP increased 3.12 µg/L or 9.35 µg/L and protein expression of K-Ras, ERK1/2 or p-ERK1/2 upregulated 0.52, 0.06 and 1.19 fold (all P < 0.05) in MVA, PTH1-34 and atrovastatin co-treated cardiomyocytes.


CONCLUSIONS
Atrovastatin attenuates PTH1-34 induced neonatal rat cardiomyocytes hypertrophy through downregulating K-Ras and ERK1/2 pathway.
Department of Nephrology, First Affiliated Hospital to Harbin Medical University, Harbin 150036, China.
Xiao-gang
XG
Liu
Nan
N
Miao
Man-shu
MS
Sui
Su-hong
SH
Mu
Shi-lei
SL
Zhao
Ru-juan
RJ
Xie
D000818:Animals; D000831:Animals, Newborn; D000069059:Atorvastatin; D006332:Cardiomegaly / Q000188:drug therapy / Q000378:metabolism*; D002478:Cells, Cultured; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D020935:MAP Kinase Signaling System; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
D006538:Heptanoic Acids; D010281:Parathyroid Hormone; D011758:Pyrroles; D000069059:Atorvastatin; D048052:Mitogen-Activated Protein Kinase 3