Telmisartan suppresses cardiomyocyte and alveolar wall hypertrophy by the PPARγ-ERK-NFAT complex by changing the balance of PPARγ and ERK

Abstract

Telmisartan inhibits cardiomyocytes by activating peroxisome proliferator-activated receptor (PPARγ), downregulating extracellular signal-regulated kinase (ERK), and inhibiting nuclear factor of activated T cells (NFAT). However, it has been unclear whether telmisartan is intrinsically associated with PPARγ, ERK, and NFAT. The present study focused on the role of telmisartan with respect to PPARγ, ERK, and NFAT. Angiotensin II was used to stimulate primary cardiomyocytes to create a cardiomyocyte hypertrophy model in vitro with increased pathologic protein synthesis and NFAT nuclear translocation. Telmisartan suppressed angiotensin II-induced cardiomyocyte hypertrophy by inhibiting protein synthesis and NFAT nuclear translocation. The inhibition by telmisartan was reversed by both a PPARγ inhibitor and ERK activator. These results indicated that PPARγ and ERK play opposing roles in regulating telmisartan inhibition of cardiomyocyte hypertrophy. When we precipitated cardiomyocyte NFAT, we found that PPARγ and ERK bind to NFAT, indicating that the PPARγ-ERK-NFAT complex mediated telmisartan inhibition of cardiomyocyte hypertrophy. In this complex, the balance of PPARγ and ERK is critical to regulate NFAT function. Finally, we created a new model to explain the mechanism by which telmisartan prevents cardiomyocyte hypertrophy.

Keywords: ERK; NFAT; PPARγ; Telmisartan; cardiomyocyte hypertrophy.