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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2019

Open Access 01-12-2019 | Cardiomyopathy | Research

mTOR pathway in human cardiac hypertrophy caused by LEOPARD syndrome: a different role compared with animal models?

Authors: Hao Cui, Lei Song, Changsheng Zhu, Ce Zhang, Bing Tang, Shengwei Wang, Guixin Wu, Yubao Zou, Xiaohong Huang, Rutai Hui, Shuiyun Wang, Jizheng Wang

Published in: Orphanet Journal of Rare Diseases | Issue 1/2019

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Abstract

Background

Animal studies suggested that blocking the activation of the mammalian target of rapamycin (mTOR) pathway might be effective to treat cardiac hypertrophy in LEOPARD syndrome (LS) caused by PTPN11 mutations.

Results

In the present study, mTOR pathway activity was examined in human myocardial samples from two patients with LS, four patients with hypertrophic cardiomyopathy (HCM), and four normal controls. The two patients with LS had p.Y279C and p.T468 M mutations of the PTPN11 gene, respectively. Although PTPN11 mutation showed initially positive regulation on phosphoinositide 3-kinase, overall the mTOR complex 1 pathway showed widely attenuated activity in LS. This included mildly hypophosphorylated mTOR and ribosomal protein S6 kinase and significantly hypophosphorylated Akt308 and ribosomal protein S6, which is similar to HCM. Akt473 is a basal molecule of the mTOR complex 2 pathway. Akt473 was less affected and showed hyperactivity in LS compared with HCM and normal controls. Additionally, MAPK/ERK kinase and ERK1/2 were significantly more phosphorylated in both HCM and LS than normal controls.

Conclusions

In LS, the mTOR signaling pathway shows similar activity to HCM and is attenuated compared with normal controls. Thus, caution should be applied when using rapamycin to treat heart hypertrophy in LS.
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Metadata
Title
mTOR pathway in human cardiac hypertrophy caused by LEOPARD syndrome: a different role compared with animal models?
Authors
Hao Cui
Lei Song
Changsheng Zhu
Ce Zhang
Bing Tang
Shengwei Wang
Guixin Wu
Yubao Zou
Xiaohong Huang
Rutai Hui
Shuiyun Wang
Jizheng Wang
Publication date
01-12-2019
Publisher
BioMed Central
Keyword
Cardiomyopathy
Published in
Orphanet Journal of Rare Diseases / Issue 1/2019
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-019-1204-4

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