期刊
ESC HEART FAILURE
卷 8, 期 3, 页码 1979-1989出版社
WILEY PERIODICALS, INC
DOI: 10.1002/ehf2.13269
关键词
Cardiac hypertrophy; CKD; PGE2; EP2; 5/6NT rats
资金
- foundation of the National Natural Science Foundation of China [81871598, 81400742]
- Shanghai science and technology innovation plan popular science projec [19DZ2321400]
- Shanghai science and technology innovation plan technical standard project [19DZ2205600]
The study showed that both EP2 and EP4 receptors were up-regulated in PGE2-treated cardiomyocyte cells, and the inhibition of EP2 receptor could suppress PGE2-induced cardiomyocyte hypertrophy and cardiac fibrosis. Additionally, EP2 receptor inhibitor administration significantly improved cardiac function and fibrosis in the 5/6NT rat model.
Aims Prostaglandin E-2 (PGE2) is involved in the development of cardiac hypertrophy. However, whether PGE2 regulates the chronic kidney disease-associated cardiac hypertrophy and the tentative mechanism remains to be elucidated. Methods and results We explored the effect of PGE2 receptor inhibitors on cardiac hypertrophy in vitro and in a 5/6 nephrectomy (5/6NT) rat model using quantitative reverse transcription polymerase chain reaction, western blotting, enzyme-linked immunosorbent assay, immunohistochemical staining, and immunofluorescence staining assays. The result showed that EP2 and EP4 receptors were both up-regulated in the PGE2-treated cardiomyocyte cells. PGE2 treatment enhanced active beta-catenin (non-phosphorylated) signalling through mediating EP2 and EP4 receptors. Interestingly, inhibition of EP2 receptor suppressed PGE2-induced cardiomyocyte hypertrophy and cardiac fibrosis-related proteins in vitro. In the 5/6NT rat model, the increased secretion PGE2 was identified in the 5/6NT rat model for 2 weeks (P = 0.0251). EP2 receptor inhibitor administration significantly improved the cardiac function and fibrosis in 5/6NT rats. Conclusions Our study demonstrated that inhibition of EP2 receptor could improve PGE2-induced cardiac hypertrophy in 5/6NT rats. The exploration of these mechanisms may contribute to the optimization of therapy in chronic kidney disease accompanied cardiac hypertrophy in clinic.
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