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Ischemic Stroke Risk Associated with Mitochondrial Haplogroup F in the Asian Population

Mitochondrial dysfunction is involved in the pathogenesis of atherosclerosis, the primary risk factor for ischemic stroke. This study aims to explore the role of mitochondrial genomic variations in ischemic stroke, and to uncover the nuclear genes involved in this relationship. Eight hundred and thi...

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Autores principales: Tsai, Meng-Han, Kuo, Chung-Wen, Lin, Tsu-Kung, Ho, Chen-Jui, Wang, Pei-Wen, Chuang, Jiin-Haur, Liou, Chia-Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463505/
https://www.ncbi.nlm.nih.gov/pubmed/32796743
http://dx.doi.org/10.3390/cells9081885
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author Tsai, Meng-Han
Kuo, Chung-Wen
Lin, Tsu-Kung
Ho, Chen-Jui
Wang, Pei-Wen
Chuang, Jiin-Haur
Liou, Chia-Wei
author_facet Tsai, Meng-Han
Kuo, Chung-Wen
Lin, Tsu-Kung
Ho, Chen-Jui
Wang, Pei-Wen
Chuang, Jiin-Haur
Liou, Chia-Wei
author_sort Tsai, Meng-Han
collection PubMed
description Mitochondrial dysfunction is involved in the pathogenesis of atherosclerosis, the primary risk factor for ischemic stroke. This study aims to explore the role of mitochondrial genomic variations in ischemic stroke, and to uncover the nuclear genes involved in this relationship. Eight hundred and thirty Taiwanese patients with a history of ischemic stroke and 966 normal controls were genotyped for their mitochondrial haplogroup (Mthapg). Cytoplasmic hybrid cells (cybrids) harboring different Mthapgs were used to observe functional differences under hypoxia-ischemia. RNA sequencing (RNASeq) was conducted to identify the particularly elevated mRNA. The patient study identified an association between Mthapg F1 and risk of ischemic stroke (OR 1.72:1.27–2.34, p = 0.001). The cellular study further demonstrated an impeded induction of hypoxic inducible factor 1α in the Mthapg F1 cybrid after hypoxia-ischemia. Additionally, the study demonstrated that Mthapg F cybrids were associated with an altered mitochondrial function, including decreased oxygen consumption, higher mitochondrial ROS production, and lower mitochondrial membrane potential. Mthapg F cybrids were also noted to be prone to inflammation, with increased expression of several inflammatory cytokines and elevated matrix metalloproteinase 9. The RNASeq identified significantly elevated expressions of angiopoietin-like 4 in Mthapg F1 cybrids after hypoxia-ischemia. Our study demonstrates an association between Mthapg F and susceptibility to ischemic stroke.
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spelling pubmed-74635052020-09-04 Ischemic Stroke Risk Associated with Mitochondrial Haplogroup F in the Asian Population Tsai, Meng-Han Kuo, Chung-Wen Lin, Tsu-Kung Ho, Chen-Jui Wang, Pei-Wen Chuang, Jiin-Haur Liou, Chia-Wei Cells Article Mitochondrial dysfunction is involved in the pathogenesis of atherosclerosis, the primary risk factor for ischemic stroke. This study aims to explore the role of mitochondrial genomic variations in ischemic stroke, and to uncover the nuclear genes involved in this relationship. Eight hundred and thirty Taiwanese patients with a history of ischemic stroke and 966 normal controls were genotyped for their mitochondrial haplogroup (Mthapg). Cytoplasmic hybrid cells (cybrids) harboring different Mthapgs were used to observe functional differences under hypoxia-ischemia. RNA sequencing (RNASeq) was conducted to identify the particularly elevated mRNA. The patient study identified an association between Mthapg F1 and risk of ischemic stroke (OR 1.72:1.27–2.34, p = 0.001). The cellular study further demonstrated an impeded induction of hypoxic inducible factor 1α in the Mthapg F1 cybrid after hypoxia-ischemia. Additionally, the study demonstrated that Mthapg F cybrids were associated with an altered mitochondrial function, including decreased oxygen consumption, higher mitochondrial ROS production, and lower mitochondrial membrane potential. Mthapg F cybrids were also noted to be prone to inflammation, with increased expression of several inflammatory cytokines and elevated matrix metalloproteinase 9. The RNASeq identified significantly elevated expressions of angiopoietin-like 4 in Mthapg F1 cybrids after hypoxia-ischemia. Our study demonstrates an association between Mthapg F and susceptibility to ischemic stroke. MDPI 2020-08-11 /pmc/articles/PMC7463505/ /pubmed/32796743 http://dx.doi.org/10.3390/cells9081885 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tsai, Meng-Han
Kuo, Chung-Wen
Lin, Tsu-Kung
Ho, Chen-Jui
Wang, Pei-Wen
Chuang, Jiin-Haur
Liou, Chia-Wei
Ischemic Stroke Risk Associated with Mitochondrial Haplogroup F in the Asian Population
title Ischemic Stroke Risk Associated with Mitochondrial Haplogroup F in the Asian Population
title_full Ischemic Stroke Risk Associated with Mitochondrial Haplogroup F in the Asian Population
title_fullStr Ischemic Stroke Risk Associated with Mitochondrial Haplogroup F in the Asian Population
title_full_unstemmed Ischemic Stroke Risk Associated with Mitochondrial Haplogroup F in the Asian Population
title_short Ischemic Stroke Risk Associated with Mitochondrial Haplogroup F in the Asian Population
title_sort ischemic stroke risk associated with mitochondrial haplogroup f in the asian population
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463505/
https://www.ncbi.nlm.nih.gov/pubmed/32796743
http://dx.doi.org/10.3390/cells9081885
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