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Basic science: Experiment research
e0198 Activity of calcineurin NFAT signalling pathway involving in remodelling in cTnI R146W mice
  1. Zhu Shushu,
  2. Ma Jizheng,
  3. Chen Xiangjian,
  4. Wu Hengfang,
  5. Yang Di,
  6. Zhang Jinan
  1. Nanjing Medical University, China

Abstract

Objective To construct a transgenic model of HCM overexpressing cTnIR146W, observe the pathological change of this animal, and elucidate the signalling pathway involving in heart remodelling of cTnIR146W +/− mice.

Methods Cardiac hypertrophy-related signalling pathway protein, such as calcineurin, calsarcin-1, GSK-3β, AKT, SERCA2, PLB were detected by Western blot and RT-PCR. We also assessed the activity of calcineurin in cTnIR146W +/− mice, in order to elucidate potential mechanisms involving in the cardiac remodelling in cTnIR146W +/− mice.

Results The total expression of cTnI in cTnIR146W +/− mice was significant higher than cTnIR146W −/− mice (p<0.05), while the phosphorylation of cTnI decreased significantly (p<0.05), resulting in a obvious decrease of the ratio of phos-cTnI to cTnI (p<0.05). Pathological changes such as myocardial cell proliferation, cardiac hypertrophy, and interstitial fibrosis were observed by optical microscope in cTnIR146W +/− mice. Markers of cardiac hypertrophy, such as ANF, BNP, β-MHC increased significantly in cTnIR146W +/− mice (p<0.05). The expression of calsarcin-1 in cTnIR146W +/− mice was significantly higher than that of cTnIR146W −/− mice (p<0.01), while other cardiac hypertrophy-related signalling pathway protein, such as calcineurin, GSK-3β, AKT, SERCA2 did not change. The mRNA expression of PLB was reduced significantly by RT-PCR (p<0.05). Meanwhile, the calcineurin activity of cTnIR146W +/− mice increased significantly (p<0.01).

Conclusion cTnIR146W +/− mice had typical pathological cardiac remodelling and heart dysfunction, especially in the older ones. The expression of calsarcin-1 and the activity of calcineurin-NFAT signalling pathway may be the most important mechanism involving in pathological cardiac hypertrophy in cTnIR146W −/− mice.

  • Hypertrophic cardiomyopathy (HCM)
  • reverse transcription PCR (RT-PCR)

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