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Cardiac troponin I autoantibody induces myocardial dysfunction by PTEN signaling activation

BACKGROUND: The objective of the current study was to study the molecular mechanism(s) underlying cardiac troponin I autoantibody (cTnIAAb) binding to cardiomyocyte and resultant myocardial damage/dysfunction. METHODS: cTnIAAb was purified from serum of 10 acute myocardial infarction (AMI) patients...

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Autores principales: Wu, Yu, Qin, Yang-hua, Liu, Yang, Zhu, Li, Zhao, Xian-xian, Liu, Yao-yang, Luo, Shi-wen, Tang, Gu-sheng, Shen, Qian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796505/
https://www.ncbi.nlm.nih.gov/pubmed/31474552
http://dx.doi.org/10.1016/j.ebiom.2019.08.045
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author Wu, Yu
Qin, Yang-hua
Liu, Yang
Zhu, Li
Zhao, Xian-xian
Liu, Yao-yang
Luo, Shi-wen
Tang, Gu-sheng
Shen, Qian
author_facet Wu, Yu
Qin, Yang-hua
Liu, Yang
Zhu, Li
Zhao, Xian-xian
Liu, Yao-yang
Luo, Shi-wen
Tang, Gu-sheng
Shen, Qian
author_sort Wu, Yu
collection PubMed
description BACKGROUND: The objective of the current study was to study the molecular mechanism(s) underlying cardiac troponin I autoantibody (cTnIAAb) binding to cardiomyocyte and resultant myocardial damage/dysfunction. METHODS: cTnIAAb was purified from serum of 10 acute myocardial infarction (AMI) patients with left ventricular remodeling. Recombinant human cTnI was used to generate three mouse-derived monoclonal anti-cTnI antibodies (cTnImAb1, cTnImAb2, and cTnImAb3). The target proteins in cardiac myocyte membrane bound to cTnImAb and effect of cTnIAAb and cTnImAb on apoptosis and myocardial function were determined. FINDINGS: We found that cTnIAAb/cTnImAb1 directly bound to the cardiomyocyte membraneα-Enolase (ENO1) and triggered cell apoptosis via increased expression of ENO1 and Bax, decreased expression of Bcl2, subsequently activating Caspase8, Caspase 3, phosphatase and tensin homolog (PTEN) while inhibiting Akt activity. This cTnIAAb-ENO1-PTEN-Akt signaling axis contributed to increased myocardial apoptosis, myocardial collagen deposition, and impaired systolic dysfunction. INTERPRETATION: Results obtained in this study indicate that cTnIAAb is involved in the process of ventricular remodeling after myocardial injury. FUND: The National Natural Science Foundation of China (Grant#: 81260026).
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spelling pubmed-67965052019-10-22 Cardiac troponin I autoantibody induces myocardial dysfunction by PTEN signaling activation Wu, Yu Qin, Yang-hua Liu, Yang Zhu, Li Zhao, Xian-xian Liu, Yao-yang Luo, Shi-wen Tang, Gu-sheng Shen, Qian EBioMedicine Research paper BACKGROUND: The objective of the current study was to study the molecular mechanism(s) underlying cardiac troponin I autoantibody (cTnIAAb) binding to cardiomyocyte and resultant myocardial damage/dysfunction. METHODS: cTnIAAb was purified from serum of 10 acute myocardial infarction (AMI) patients with left ventricular remodeling. Recombinant human cTnI was used to generate three mouse-derived monoclonal anti-cTnI antibodies (cTnImAb1, cTnImAb2, and cTnImAb3). The target proteins in cardiac myocyte membrane bound to cTnImAb and effect of cTnIAAb and cTnImAb on apoptosis and myocardial function were determined. FINDINGS: We found that cTnIAAb/cTnImAb1 directly bound to the cardiomyocyte membraneα-Enolase (ENO1) and triggered cell apoptosis via increased expression of ENO1 and Bax, decreased expression of Bcl2, subsequently activating Caspase8, Caspase 3, phosphatase and tensin homolog (PTEN) while inhibiting Akt activity. This cTnIAAb-ENO1-PTEN-Akt signaling axis contributed to increased myocardial apoptosis, myocardial collagen deposition, and impaired systolic dysfunction. INTERPRETATION: Results obtained in this study indicate that cTnIAAb is involved in the process of ventricular remodeling after myocardial injury. FUND: The National Natural Science Foundation of China (Grant#: 81260026). Elsevier 2019-08-29 /pmc/articles/PMC6796505/ /pubmed/31474552 http://dx.doi.org/10.1016/j.ebiom.2019.08.045 Text en © 2019 Published by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research paper
Wu, Yu
Qin, Yang-hua
Liu, Yang
Zhu, Li
Zhao, Xian-xian
Liu, Yao-yang
Luo, Shi-wen
Tang, Gu-sheng
Shen, Qian
Cardiac troponin I autoantibody induces myocardial dysfunction by PTEN signaling activation
title Cardiac troponin I autoantibody induces myocardial dysfunction by PTEN signaling activation
title_full Cardiac troponin I autoantibody induces myocardial dysfunction by PTEN signaling activation
title_fullStr Cardiac troponin I autoantibody induces myocardial dysfunction by PTEN signaling activation
title_full_unstemmed Cardiac troponin I autoantibody induces myocardial dysfunction by PTEN signaling activation
title_short Cardiac troponin I autoantibody induces myocardial dysfunction by PTEN signaling activation
title_sort cardiac troponin i autoantibody induces myocardial dysfunction by pten signaling activation
topic Research paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796505/
https://www.ncbi.nlm.nih.gov/pubmed/31474552
http://dx.doi.org/10.1016/j.ebiom.2019.08.045
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