Upregulation of CFTR Protects against Palmitate-Induced Endothelial Dysfunction by Enhancing Autophagic Flux
Joint Authors
Chen, Hongqi
Chen, Wenliang
Yao, Yinlian
Ye, Naobei
Hou, Ning
Luo, Jiandong
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-17, 17 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-10-17
Country of Publication
Egypt
No. of Pages
17
Main Subjects
Abstract EN
Saturated free fatty acids (FFAs) elevate in metabolic symptom leading to endothelial dysfunction.
Cystic fibrosis transmembrane regulator (CFTR) functionally expresses in endothelial cells.
The role of CFTR in FFA-induced endothelial dysfunction remains unclear.
This study is aimed at exploring the effects of CFTR on palmitate- (PA-) induced endothelial dysfunction and its underlying mechanisms.
We found that PA-induced endothelial dysfunction is characterized by a decrease of cell viability, reduction of NO generation and mitochondrial membrane potential, impairment of the tube formation, but an increase of ROS generation and cell apoptosis.
Simultaneously, PA decreased CFTR protein expression.
CFTR agonist Forskolin upregulated CFTR protein expression and protected against PA-induced endothelial dysfunction, while CFTR knockdown exacerbated endothelial dysfunction induced by PA and blunted the protective effects of Forskolin.
In addition, PA impaired autophagic flux, and autophagic flux inhibitors aggravated PA-induced endothelial apoptosis.
CFTR upregulation significantly restored autophagic flux in PA-insulted endothelial cells, which was involved in increasing the protein expression of Atg16L, Atg12-Atg5 complex, cathepsin B, and cathepsin D.
In contrast, CFTR knockdown significantly inhibited the effects of Forskolin on autophagic flux and the expression of the autophagy-regulated proteins.
Our findings illustrate that CFTR upregulation protects against PA-induced endothelial dysfunction by improving autophagic flux and underlying mechanisms are involved in enhancing autophagic signaling mediated by the Atg16L-Atg12-Atg5 complex, cathepsin B, and cathepsin D.
CFTR might serve as a novel drug target for endothelial protection in cardiovascular diseases with a characteristic of elevation of FFAs.
American Psychological Association (APA)
Chen, Hongqi& Chen, Wenliang& Yao, Yinlian& Ye, Naobei& Hou, Ning& Luo, Jiandong. 2020. Upregulation of CFTR Protects against Palmitate-Induced Endothelial Dysfunction by Enhancing Autophagic Flux. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-17.
https://search.emarefa.net/detail/BIM-1205578
Modern Language Association (MLA)
Chen, Hongqi…[et al.]. Upregulation of CFTR Protects against Palmitate-Induced Endothelial Dysfunction by Enhancing Autophagic Flux. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-17.
https://search.emarefa.net/detail/BIM-1205578
American Medical Association (AMA)
Chen, Hongqi& Chen, Wenliang& Yao, Yinlian& Ye, Naobei& Hou, Ning& Luo, Jiandong. Upregulation of CFTR Protects against Palmitate-Induced Endothelial Dysfunction by Enhancing Autophagic Flux. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-17.
https://search.emarefa.net/detail/BIM-1205578
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1205578