How does NFAT3 regulate the occurrence of cardiac hypertrophy?

Abstract

Cardiac hypertrophy is initially an adaptive response to physiological and pathological stimuli. Although pathological myocardial hypertrophy is the main cause of morbidity and mortality, our understanding of its mechanism is still weak. NFAT3 (nuclear factor of activated T-cell-3) is a member of the nuclear factor of the activated T cells (NFAT) family. NFAT3 plays a critical role in regulating the expression of cardiac hypertrophy genes by inducing their transcription. Recently, accumulating evidence has indicated that NFAT3 is a potent regulator of the progression of cardiac hypertrophy. This review, for the first time, summarizes the current studies on NFAT3 in cardiac hypertrophy, including the pathophysiological processes and the underlying pathological mechanism, focusing on the nuclear translocation and transcriptional function of NFAT3. This review will provide deep insight into the pathogenesis of cardiac hypertrophy and a theoretical basis for identifying new therapeutic targets in the NFAT3 network.

Keywords: Cardiac hypertrophy; NFAT3; Nuclear translocation.

Fig. 1

General structure of the NFAT protein. NFAT proteins consist of an NHR, a DNA-binding domain (RHD) and a carboxy-terminal domain. The regulatory domain contains an N-terminal transactivation domain (TAD), as well as a docking site for casein kinase 1 (CK1), termed FSILF, and for calcineurin, termed SPRIEIT. The regulatory domain also includes multiple serine-rich motifs (SRR1, SP1, SP2, SRR2, SP3 and KTS) and a nuclear localization sequence (NLS).

Fig. 2

Role and potential mechanism of NFAT3 and its targets in cardiac hypertrophy. CaN, p38, ERK5, IRAK-1, AP-1, CBP, GATA4, NULP1, Lipin-1, PARP-1, PGC-1α, 14-3-3, and mTOR.