Myotubularin-related protein 14 suppresses cardiac hypertrophy by inhibiting Akt

Jie-Lei Zhang,Zheng Wang,Ya-Peng Li,Rui Yao,Dian-Hong Zhang,Lei-Ming Wu,Zhong-Min Wang,Sheng-Dong Feng,Yan-Zhou Zhang,Cui Liang

doi:10.1038/s41419-020-2330-6

Abstract

Cardiac hypertrophy (CH) is an independent risk factor for many cardiovascular diseases, and is one of the primary causes of morbidity and mortality in elderly people. Pathological CH involves excessive protein synthesis, increased cardiomyocyte size, and ultimately the development of heart failure. Myotubularin-related protein 14 (MTMR14) is a member of the myotubularin (MTM)-related protein family, which is involved in apoptosis, aging, inflammation, and autophagy. However, its exact function in CH is still unclear. Herein, we investigated the roles of MTMR14 in CH. We show that MTMR14 expression was increased in hypertrophic mouse hearts. Mice deficient in heart MTMR14 exhibited an aggravated aortic-banding (AB)-induced CH phenotype. In contrast, MTMR14 overexpression prevented pressure overload-induced hypertrophy. At the molecular level, prevention of CH in the absence of MTMR14 involved elevations in Akt pathway components, which are key elements that regulate apoptosis and cell proliferation. These results demonstrate that MTMR14 is a new molecular target for the treatment of CH.

Highlights

Cardiac hypertrophy (CH) represents an adaptive response of the heart to an increased workload, and is a well-established risk factor for cardiovascular mortality worldwide[1]
MTMR14 protein levels were upregulated in the hearts of the hypertrophy models at 4 weeks after AB surgery compared with the hearts of the sham-operated mice
The levels of the fetal gene ANP increased in the model mice, as assessed by Western blotting. The levels of both MTMR14 and ANP were upregulated in isolated Neonatal rat cardiomyocytes (NRCMs) that were treated with angiotensin II (Ang II) for 24 compared with phosphate-buffered saline (PBS)-treated control

Summary

Introduction

Cardiac hypertrophy (CH) represents an adaptive response of the heart to an increased workload, and is a well-established risk factor for cardiovascular mortality worldwide[1]. CH is primarily characterized by excess protein synthesis, increased cardiomyocyte size, and thickened ventricular walls and is a major risk factor that promotes arrhythmia and heart failure[3]. Consistent with these characteristics, pathologic CH plays a compensatory role. Several mechanisms have been highlighted as potential contributors to the etiopathogenesis of CH, mostly based on common knowledge of pressure overload regulation. The aforementioned signaling pathways have been extensively characterized in pressure overload, improving our understanding of the mechanisms responsible for CH is important, and new molecular pathways involved in Official journal of the Cell Death Differentiation Association

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Conclusion