How Does NFAT3 Regulate the Occurrence of Cardiac Hypertrophy?

Overview

Journal Int J Cardiol Heart Vasc

Date 2023 Sep 27

PMID 37753338

Authors

Wang Hui

Su Wenhua

Zhang Shuojie

Wang Lulin

Zhao Panpan

Zhang Tongtong

Xie Xiaoli

Dan Juhua

Affiliations

Soon will be listed here.

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.

References

Maillet M, van Berlo J, Molkentin J . Molecular basis of physiological heart growth: fundamental concepts and new players. Nat Rev Mol Cell Biol. 2012; 14(1):38-48. PMC: 4416212. DOI: 10.1038/nrm3495. View

Kalkan Y, Tumkaya L, Bostan H, Tomak Y, Yilmaz A . Effects of sugammadex on immunoreactivity of calcineurin in rat testes cells after neuromuscular block: a pilot study. J Mol Histol. 2011; 43(2):235-41. DOI: 10.1007/s10735-011-9384-9. View

Su F, Shi M, Zhang J, Li Y, Tian J . Recombinant high‑mobility group box 1 induces cardiomyocyte hypertrophy by regulating the 14‑3‑3η, PI3K and nuclear factor of activated T cells signaling pathways. Mol Med Rep. 2021; 23(3). PMC: 7845624. DOI: 10.3892/mmr.2021.11853. View

Steen H, Lindholm D . Nuclear localized protein-1 (Nulp1) increases cell death of human osteosarcoma cells and binds the X-linked inhibitor of apoptosis protein. Biochem Biophys Res Commun. 2007; 366(2):432-7. DOI: 10.1016/j.bbrc.2007.11.146. View

Hogan P, Chen L, Nardone J, Rao A . Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev. 2003; 17(18):2205-32. DOI: 10.1101/gad.1102703. View

Tu V, Sun H, Bowden G, Chen Q . Involvement of oxidants and AP-1 in angiotensin II-activated NFAT3 transcription factor. Am J Physiol Cell Physiol. 2006; 292(4):C1248-55. DOI: 10.1152/ajpcell.00624.2005. View

Rusnak F, Mertz P . Calcineurin: form and function. Physiol Rev. 2000; 80(4):1483-521. DOI: 10.1152/physrev.2000.80.4.1483. View

Klemm J, Beals C, Crabtree G . Rapid targeting of nuclear proteins to the cytoplasm. Curr Biol. 1997; 7(9):638-44. DOI: 10.1016/s0960-9822(06)00290-9. View

Yaghi A, Sims S . Constrictor-induced translocation of NFAT3 in human and rat pulmonary artery smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2005; 289(6):L1061-74. DOI: 10.1152/ajplung.00096.2005. View

10.

Rincon M, Flavell R . Transcription mediated by NFAT is highly inducible in effector CD4+ T helper 2 (Th2) cells but not in Th1 cells. Mol Cell Biol. 1997; 17(3):1522-34. PMC: 231878. DOI: 10.1128/MCB.17.3.1522. View

11.

Shati A . Doxorubicin-induces NFAT/Fas/FasL cardiac apoptosis in rats through activation of calcineurin and P38 MAPK and inhibition of mTOR signalling pathways. Clin Exp Pharmacol Physiol. 2019; 47(4):660-676. DOI: 10.1111/1440-1681.13225. View

12.

Li R, Zhang L, Shi W, Zhang B, Liang X, Liu S . NFAT2 mediates high glucose-induced glomerular podocyte apoptosis through increased Bax expression. Exp Cell Res. 2013; 319(7):992-1000. DOI: 10.1016/j.yexcr.2013.01.007. View

13.

Debosch B, Treskov I, Lupu T, Weinheimer C, Kovacs A, Courtois M . Akt1 is required for physiological cardiac growth. Circulation. 2006; 113(17):2097-104. DOI: 10.1161/CIRCULATIONAHA.105.595231. View

14.

Benedito A, Lehtinen M, Massol R, Gazos Lopes U, Kirchhausen T, Rao A . The transcription factor NFAT3 mediates neuronal survival. J Biol Chem. 2004; 280(4):2818-25. DOI: 10.1074/jbc.M408741200. View

15.

Zeitz M, Smyth J . Translating Translation to Mechanisms of Cardiac Hypertrophy. J Cardiovasc Dev Dis. 2020; 7(1). PMC: 7151157. DOI: 10.3390/jcdd7010009. View

16.

Tu V, Bahl J, Chen Q . Distinct roles of p42/p44(ERK) and p38 MAPK in oxidant-induced AP-1 activation and cardiomyocyte hypertrophy. Cardiovasc Toxicol. 2003; 3(2):119-33. DOI: 10.1385/ct:3:2:119. View

17.

Wang C, Li J, Zhao L, Liu J, Wan J, Wang Y . Inhibition of SOC/Ca2+/NFAT pathway is involved in the anti-proliferative effect of sildenafil on pulmonary artery smooth muscle cells. Respir Res. 2009; 10:123. PMC: 2797778. DOI: 10.1186/1465-9921-10-123. View

18.

Ram B, Dolpady J, Kulkarni R, Usha R, Bhoria U, Poli U . Human papillomavirus (HPV) oncoprotein E6 facilitates Calcineurin-Nuclear factor for activated T cells 2 (NFAT2) signaling to promote cellular proliferation in cervical cell carcinoma. Exp Cell Res. 2017; 362(1):132-141. DOI: 10.1016/j.yexcr.2017.11.010. View

19.

Yang D, Ma S, Tan Y, Li D, Tang B, Chen J . Adrenergic receptor blockade-induced regression of pressure-overload cardiac hypertrophy is associated with inhibition of the calcineurin/NFAT3/GATA4 pathway. Mol Med Rep. 2011; 3(3):497-501. DOI: 10.3892/mmr_00000287. View

20.

Tu V, Bahl J, Chen Q . Signals of oxidant-induced cardiomyocyte hypertrophy: key activation of p70 S6 kinase-1 and phosphoinositide 3-kinase. J Pharmacol Exp Ther. 2002; 300(3):1101-10. DOI: 10.1124/jpet.300.3.1101. View