NLRC5 enhances autophagy via inactivation of AKT/mTOR pathway and ameliorates cardiac hypertrophy

2021 ◽  
Author(s):  
Bayinsilema Ba ◽  
Abudoukelimu Mayila ◽  
Yankai Guo ◽  
Jie Xu ◽  
Shifeng Xing ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Mtor Pathway

GPR39 promotes cardiac hypertrophy by regulating the AMPK‐mTOR pathway and protein synthesis

2021 ◽  
Author(s):  
Hongjuan Liao ◽  
Weinian Gao ◽  
Jie Ma ◽  
Hongyuan Xue ◽  
Yi Wang ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Cardiac Hypertrophy ◽  
Mtor Pathway

Abstract 076: Lapatinib Reduced Cardiac Hypertrophy Induced By Combined Use Of A Pi3k-mtor Dual Inhibitor And Doxorubicin

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Xinhua Yan ◽  
Yongyao Yang ◽  
Juyong Lee ◽  
Jillian Onufrak ◽  
John Fuseler ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Cardiac Effect ◽  
Mtor Pathway ◽  
Dual Inhibitor ◽  
Cardiac Side Effects ◽  
Compound C ◽  
Transmission Electron ◽  
Combined Use ◽  
Cardioprotective Effects ◽  
Lapatinib Treatment

The HER2-PI3K-mTOR pathway is pivotal for regulating the physiological function of the heart. Currently, drugs targeting the HER2-PI3K-mTOR pathway are either approved or being tested in clinical trials for cancer therapy. It is, therefore, important to evaluate the cardiac effects of using these drugs. In addition, it is necessary to develop countermeasures to prevent the cardiac side effects if any. Methods: Three-month old female FVB/n mice were treated with lapatinib (an HER2 inhibitor) or BEZ235 (BEZ, a PI3K-mTOR dual inhibitor), alone or with doxorubicin (DOX). Cardiac function was monitored by echocardiography and hemodynamic measurements. Cardiac morphology was assessed by confocal microscopy and transmission electron microscopy. The activation of signaling molecules were measured by Western blot analysis. Results: BEZ alone induced cardiac hypertrophy and subsequent heart failure and lapatinib alone induced cardiac failure, in a course of 17 months, respectively. Combination of BEZ with DOX, either concurrently or sequentially, induced cardiac hypertrophy which was associated with higher mortality rate compared to DOX alone. Neuregulin1, a HER receptor ligand worsened, while Lapatinib alleviated, cardiac hypertrophy in these mice. Lapatinib increased the activation of AMPK in DOX+BEZ treated hearts. The cardiac effect of lapatinib was blocked by Compound C, an AMPK inhibitor. Metformin, an AMPK activator, alleviated DOX+BEZ induced cardiac hypertrophy. Conclusions: BEZ or lapatinib treatment alone induced irreversible cardiac dysfunction in mice. Combined use of BEZ and DOX induced cardiac hypertrophy and early mortality, which were prevented by lapatinib. The cardioprotective effects of lapatinib may rely on activating AMPK in the heart.

scholarly journals YQFM alleviated cardiac hypertrophy by apoptosis inhibition and autophagy regulation via PI3K/AKT/mTOR pathway

2021 ◽  
pp. 114835
Author(s):  
Meixu Wan ◽  
Kunkun Yin ◽  
Jing Yuan ◽  
Shiyan Ma ◽  
Qing Xu ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Mtor Pathway ◽  
Apoptosis Inhibition

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

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Hao Cui ◽  
Lei Song ◽  
Changsheng Zhu ◽  
Ce Zhang ◽  
Bing Tang ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Ribosomal Protein ◽  
Animal Studies ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Pathway ◽  
Leopard Syndrome ◽  
Ribosomal Protein S6 ◽  
Phosphoinositide 3 Kinase ◽  
Mtor Complex 1 ◽  
Normal Controls

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.

scholarly journals Nitrite exerts antioxidant effects, inhibits the mTOR pathway and reverses hypertension-induced cardiac hypertrophy

2018 ◽  
Vol 120 ◽  
pp. 25-32 ◽  
Author(s):  
Danielle A. Guimaraes ◽  
Madla A. dos Passos ◽  
Elen Rizzi ◽  
Lucas C. Pinheiro ◽  
Jefferson H. Amaral ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Mtor Pathway ◽  
Antioxidant Effects

Resveratrol prevents chronic intermittent hypoxia-induced cardiac hypertrophy by targeting the PI3K/AKT/mTOR pathway

Life Sciences ◽  
2019 ◽  
Vol 233 ◽  
pp. 116748 ◽  
Author(s):  
Peng Guan ◽  
Zhi-Min Sun ◽  
Na Wang ◽  
Jian Zhou ◽  
Li-Fei Luo ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Intermittent Hypoxia ◽  
Mtor Pathway ◽  
Chronic Intermittent Hypoxia

scholarly journals PKD knockdown inhibits pressure overload-induced cardiac hypertrophy by promoting autophagy via AKT/mTOR pathway

2017 ◽  
Vol 13 (3) ◽  
pp. 276-285 ◽  
Author(s):  
Di Zhao ◽  
Wei Wang ◽  
Hao Wang ◽  
Honghai Peng ◽  
Xiangjuan Liu ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Pressure Overload ◽  
Mtor Pathway
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