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[Atorvastatin attenuates parathyroid hormone 1-34 induced cardiomyocytes hypertrophy through downregulating
Xiao-gang Liu1, Nan Miao, Man-shu Sui
1Department of Nephrology, First Affiliated Hospital to Harbin Medical University, Harbin 150036, China.
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.
Insights
Atorvastatin reduces parathyroid hormone (PTH1-34) induced neonatal rat cardiomyocyte hypertrophy. This effect is mediated by downregulating the K-Ras and ERK1/2 signaling pathways, offering potential therapeutic insights.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Pharmacology
Background:
- Neonatal rat cardiomyocytes are susceptible to hypertrophy induced by parathyroid hormone 1-34 (PTH1-34).
- Hypertrophy involves cellular growth and altered protein synthesis, impacting cardiac function.
- The K-Ras and ERK1/2 signaling pathways are implicated in cellular growth and differentiation.
Purpose of the Study:
- To investigate the inhibitory effects of atorvastatin on PTH1-34 induced neonatal rat cardiomyocyte hypertrophy.
- To examine the impact of atorvastatin on the expression of K-Ras and ERK1/2 in cardiomyocytes.
- To elucidate the molecular mechanisms underlying atorvastatin's action on cardiomyocyte hypertrophy.
Main Methods:
- Neonatal rat cardiomyocytes were induced to hypertrophy using PTH1-34.
- Atorvastatin and mevalonic acid (MVA) were used to modulate the hypertrophic response.
- Cardiomyocyte size, protein synthesis rate, protein content, and biomarker concentrations (ANP, BNP) were measured.
- Western blotting was employed to detect protein expression levels of K-Ras, ERK1/2, and p-ERK1/2.
Main Results:
- Atorvastatin significantly reduced cardiomyocyte diameter, protein synthesis, and protein content compared to PTH1-34 alone.
- Co-treatment with atorvastatin decreased ANP and BNP concentrations and downregulated K-Ras, ERK1/2, and p-ERK1/2 expression.
- Mevalonic acid reversed the effects of atorvastatin, indicating a pathway-specific action.
Conclusions:
- Atorvastatin effectively attenuates PTH1-34 induced neonatal rat cardiomyocyte hypertrophy.
- The cardioprotective effect of atorvastatin is associated with the downregulation of the K-Ras and ERK1/2 signaling pathways.
- These findings suggest a potential therapeutic role for atorvastatin in managing cardiac hypertrophy.
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