Lercanidipine attenuates angiotensin II-induced cardiomyocyte hypertrophy by blocking calcineurin-NFAT3 and CaMKII-HDAC4 signaling
| Autor: | Yuezhang Chen, Jie Yuan, Qianzhou Lv, Guoliang Jiang, Yunzeng Zou, Jianbing Zhu |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Dihydropyridines cardiomyocyte hypertrophy Cancer Research medicine.medical_specialty Cell signaling FK506 Cardiomegaly Biology Biochemistry Histone Deacetylases histone deacetylase 4 Muscle hypertrophy 03 medical and health sciences Atrial natriuretic peptide Internal medicine Ca2+/calmodulin-dependent protein kinase Natriuretic Peptide Brain Genetics medicine Animals Myocytes Cardiac Molecular Biology Cells Cultured NFATC Transcription Factors calcium/calmodulin-dependent kinase II Angiotensin II Calcineurin Lercanidipine lercanidipine Articles Calcium Channel Blockers Rats nuclear factor of activated T cells 3 030104 developmental biology Endocrinology Gene Expression Regulation Oncology Molecular Medicine Signal transduction Calcium-Calmodulin-Dependent Protein Kinase Type 2 Atrial Natriuretic Factor Signal Transduction medicine.drug |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| Popis: | Previous studies have demonstrated that lercanidipine, a calcium channel blocker, may protect against cardiac hypertrophy; however, the underlying mechanisms remain unclear. In the present study, the effects of lercanidipine on hypertrophy and the mechanisms involved were investigated. Cardiomyocytes isolated from neonatal rats were cultured and treated with angiotensin II (Ang II) in the presence or absence of lercanidipine or tacrolimus (FK506, a calcineurin inhibitor). Reverse transcription‑quantitative polymerase chain reaction was used to assess the mRNA expression of genes of interest, whereas the protein expression of calcium‑dependent signaling molecules was detected using western blot analysis. In addition, the cell surface area and the nuclear translocation of target proteins were evaluated using immunofluorescence. The results of the present study demonstrated that lercanidipine and FK506 inhibited Ang II‑induced cardiomyocyte hypertrophy, as evidenced by decreases in fetal gene (atrial natriuretic peptide and brain natriuretic peptide) expression levels and cell surface area. Notably, lercanidipine suppressed Ang II‑induced activation of calcineurin A (CnA) and nuclear factor of activated T cells 3 (NFAT3). In addition, calcium/calmodulin‑dependent kinase II (CaMKII)‑histone deacetylase 4 (HDAC4) signaling was also inhibited by lercanidipine. In conclusion, the present study demonstrated that lercanidipine may ameliorate cardiomyocyte hypertrophy, possibly partially by blocking Cn-NFAT3 and CaMKII-HDAC4 signaling. |
| Databáze: | OpenAIRE |
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