Activation of transient receptor potential vanilloid 3 channel (TRPV3) aggravated pathological cardiac hypertrophy via calcineurin/NFATc3 pathway in rats.

Qianhui Zhang,Hanping Qi,Yonggang Cao,Shuzhi Li,Yunping Chen,Chao Song,Hongli Sun,Lina Ba,Pilong Shi,Baiyan Li,Jingquan Gao

doi:10.1111/jcmm.13880

Abstract

Cardiac hypertrophy is a compensatory response to mechanical stimuli and neurohormonal factors, ultimately progresses to heart failure. The proteins of some transient receptor potential (TRP) channels, Ca2+‐permeable nonselective cation channel, are highly expressed in cardiomyocytes, and associated with the occurrence of cardiac hypertrophy. Transient receptor potential vanilloid 3 (TRPV3) is a member of TRP, however, the functional role of TRPV3 in cardiac hypertrophy remains unclear. TRPV3 was elevated in pathological cardiac hypertrophy, but not in swimming exercise‐induced physiological cardiac hypertrophy in rats. TRPV3 expression was also increased in Ang II–induced cardiomyocyte hypertrophy in vitro, which was remarkably increased by carvacrol (a nonselective TRPV channel agonist), and reduced by ruthenium red (a nonselective TRPV channel antagonist). Interestingly, we found that activated TRPV3 in Ang II–induced cardiomyocyte hypertrophy was accompanied with increasing intracellular calcium concentration, promoting calcineurin, and phosphorylated CaMKII protein expression, and enhancing NFATc3 nuclear translocation. However, blocking or knockdown of TRPV3 could inhibit the expressions of calcineurin, phosphorylated CaMKII and NFATc3 protein by Western blot. In conclusion, the activation of TRPV3 aggravated pathological cardiac hypertrophy through calcineurin/NFATc3 signalling pathway and correlated with the protein expression levels of calcineurin, phosphorylated CaMKII and NFATc3, revealing that TRPV3 might be a potential therapeutic target for cardiac hypertrophy.

Highlights

Cardiac hypertrophy is a compensatory response to mechanical stimuli and neurohormonal factors
In view of Transient receptor potential vanilloid 3 (TRPV3) being a nonselective cation channel,[7] whether it is permeable to Ca2+, and contributes to cardiac hypertrophy via calcineurin/NFAT signaling pathway, we aimed to investigate the effects of TRPV3 in pressure overload‐induced cardiac hypertrophy, and to clarify the relationship between TRPV3 activation and calcineurin/NFAT pathway
To our knowledge, we demonstrated, for the first time, that the expression of TRPV3 was increased in pathological cardiac hypertrophy

Summary

| INTRODUCTION

Cardiac hypertrophy is a compensatory response to mechanical stimuli and neurohormonal factors. Several signal‐transduction pathways contributed to the hypertrophic process have been studied in recent years, it is still not fully to clear underlying molecular mechanisms for cardiac hypertrophy. Calcineurin/nuclear factor of activated T cell (NFAT) pathway plays a key role in electrical remodelling in pathological cardiac hypertrophy. Increased Ca2+ levels activate calcineurin, which binds to transcription factors of the nuclear factor of activated T cell c3 (NFATc3) Upon binding, it dephosphorylates NFATc3 to the nucleus and activates pro‐hypertrophic genes expression.[8]. In view of TRPV3 being a nonselective cation channel,[7] whether it is permeable to Ca2+, and contributes to cardiac hypertrophy via calcineurin/NFAT signaling pathway, we aimed to investigate the effects of TRPV3 in pressure overload‐induced cardiac hypertrophy, and to clarify the relationship between TRPV3 activation and calcineurin/NFAT pathway

| Ethics statement

| RESULTS

| DISCUSSION

Findings

CONFLICT OF INTEREST