An Adenosine A1 Agonist 2-Chloro-N6 Cyclopentyladenosine Inhibits the Angiotensin II-Induced Cardiomyocyte Hypertrophy through the Calcineurin Pathway

作者：Zhang, Xingliang; Xia, Juan; Qian, Dandan; Wang, Yang; Lin, Yongwen; Huang, Xiulan; Tan, Jianxin^*

来源：Cardiology, 2014, 129(3): 153-162.

DOI：10.1159/000364995

• 2-Chloro-N6 cyclopentyladenosine
• Calcineurin A beta
• Cardiomyocyte hypertrophy
• Angiotensin II

Objectives: The aim of this investigation was to study the underlying mechanism of an adenosine A(1) receptor agonist 2-chloro-N6 cyclopentyladenosine (CCPA) inhibiting cardiomyocyte hypertrophy induced by angiotensin II (AngII). @@@ Methods: Neonatal rat cardiomyocytes were treated with AngII to generate a cardiomyocyte hypertrophy model. Cardiomyocyte cultures were randomized into 5 groups: control; AngII; AngII + cyclosporin A (CsA); AngII + CCPA, and AngII + CCPA + DPCPX. Cardiomyocyte viability was measured by MTT assay. Protein synthesis was assessed by the application of H-3 leucine (H-3-Leu) incorporation into protein. The mRNA expressions of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), beta-myosin heavy chain (beta-MHC) and calcineurin A beta (CnA beta) were measured by realtime quantitative PCR. The protein level of CnA beta was dissected by Western blotting. @@@ Results: AngII administration at lower concentrations increased the cardiomyocytes viabilities gradually. Surface area, mRNA expressions of ANP, BNP and beta-MHC, and H-3-Leu incorporation of AngII-induced cardiomyocytes were increased in a dose-dependent manner. As a calcineurin-specific inhibitor, CsA inhibited H-3-Leu incorporation, surface area, mRNA expressions of ANP, BNP, beta-MHC, CnA beta and protein expression of CnA beta of AngII-induced cardiomyocytes. CCPA also suppressed the mRNA and protein expressions of CnA beta and exerted anti hypertrophic effects to a greater degree than CsA. The inhibition of CCPA on cardiomyocyte hypertrophy was counteracted by the A(1) receptor antagonist DPCPX. @@@ Conclusion: The A(1) receptor agonist CCPA could significantly inhibit AngII-induced cardiomyocyte hypertrophy via the calcineurin signaling pathway.

• 出版日期2014
• 单位广东医科大学