Mitochondrial 3243A > G mutation confers pro-atherogenic and pro-inflammatory properties in MELAS iPS derived endothelial cells.

Content Provider	Europe PMC
Author	Pek, Nicole Min Qian Phua, Qian Hua Ho, Beatrice Xuan Pang, Jeremy Kah Sheng Hor, Jin-Hui An, Omer Yang, Henry He Yu, Yang Fan, Yong Ng, Shi-Yan Soh, Boon-Seng
Abstract	Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a mitochondrial disorder that is commonly caused by the m.3243A > G mutation in the MT-TL1 gene encoding for mitochondrial tRNA(Leu(UUR)). While clinical studies reported cerebral infarcts, atherosclerotic lesions, and altered vasculature and stroke-like episodes (SLE) in MELAS patients, it remains unclear how this mutation causes the onset and subsequent progression of the disease. Here, we report that in addition to endothelial dysfunction, diseased endothelial cells (ECs) were found to be pro-atherogenic and pro-inflammation due to high levels of ROS and Ox-LDLs, and high basal expressions of VCAM-1, in particular isoform b, respectively. Consistently, more monocytes were found to adhere to MELAS ECs as compared to the isogenic control, suggesting the presence of an atherosclerosis-like pathology in MELAS. Notably, these disease phenotypes in endothelial cells can be effectively reversed by anti-oxidant treatment suggesting that the lowering of ROS is critical for treating patients with MELAS syndrome.
Journal	Cell Death & Disease
Volume Number	10
PubMed Central reference number	PMC6805858
Issue Number	11
PubMed reference number	31641105
e-ISSN	20414889
DOI	10.1038/s41419-019-2036-9
Language	English
Publisher	Nature Publishing Group
Publisher Date	2019-10-22
Publisher Place	London
Access Restriction	Open
Rights License	Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2019
Subject Keyword	Induced pluripotent stem cells Atherosclerosis Stroke Chronic inflammation
Content Type	Text
Resource Type	Article
Subject	Cell Biology Immunology Cellular and Molecular Neuroscience Medicine Cancer Research