Cathepsin C Is Involved in Macrophage M1 Polarization via p38/MAPK Pathway in Sudden Cardiac Death

This study was aimed at identifying molecular markers associated with the pathogenesis of sudden cardiac death (SCD). It provides a proteomic analysis of human left anterior descending coronary artery from subjects diagnosed with SCD through histological examination and cases of nondisease accidenta...

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Main Authors: Jialin Dai, Jiangjin Liu, Qiong Zhang, Yang An, Bing Xia, Changwu Wan, Yuanyuan Zhang, Yanni Yu, Jie Wang
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Cardiovascular Therapeutics
Online Access:http://dx.doi.org/10.1155/2021/6139732
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author Jialin Dai
Jiangjin Liu
Qiong Zhang
Yang An
Bing Xia
Changwu Wan
Yuanyuan Zhang
Yanni Yu
Jie Wang
author_facet Jialin Dai
Jiangjin Liu
Qiong Zhang
Yang An
Bing Xia
Changwu Wan
Yuanyuan Zhang
Yanni Yu
Jie Wang
author_sort Jialin Dai
collection DOAJ
description This study was aimed at identifying molecular markers associated with the pathogenesis of sudden cardiac death (SCD). It provides a proteomic analysis of human left anterior descending coronary artery from subjects diagnosed with SCD through histological examination and cases of nondisease accidental deaths through autopsy. A total of 2784 proteins were obtained from label-free quantitative proteomic analysis. This included a total of 265 differential proteins which were involved in SCD-related processes, such as inflammation, muscle system process regulation, metal ion transport, and lysosomal pathway. Western blotting was carried out to measure the expressions of cathepsin C (CTSC), focal adhesion kinase (FAK), p-FAK, and proteins related to the p38/MAPK signaling pathway, whereas immunohistochemistry was performed to determine the localization and expression of CTSC, TNF-α, and CD206 in arterial tissues. It was found that CTSC were the most expressed proteins with a significant upward trend in SCD cases. Besides, CTSC regulated macrophage polarization to M1 through the FAK-induced p38/MAPK signaling pathway. This promoted the release of inflammatory factors and eventually increased the inflammatory response. In conclusion, this study implies that CTSC may be one of the key molecular targets for promoting macrophage M1 polarization in SCD, which may provide new therapeutic insights into the treatment of inflammatory diseases.
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institution Kabale University
issn 1755-5914
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language English
publishDate 2021-01-01
publisher Wiley
record_format Article
series Cardiovascular Therapeutics
spelling doaj-art-72ba453c98a247eeba245e6ddb016b222025-02-03T01:04:33ZengWileyCardiovascular Therapeutics1755-59141755-59222021-01-01202110.1155/2021/61397326139732Cathepsin C Is Involved in Macrophage M1 Polarization via p38/MAPK Pathway in Sudden Cardiac DeathJialin Dai0Jiangjin Liu1Qiong Zhang2Yang An3Bing Xia4Changwu Wan5Yuanyuan Zhang6Yanni Yu7Jie Wang8School of Forensic Medicine, Guizhou Medical University, 4 Beijing Road, Guiyang, 550001 Guizhou, ChinaSchool of Forensic Medicine, Guizhou Medical University, 4 Beijing Road, Guiyang, 550001 Guizhou, ChinaSchool of Forensic Medicine, Guizhou Medical University, 4 Beijing Road, Guiyang, 550001 Guizhou, ChinaSchool of Forensic Medicine, Guizhou Medical University, 4 Beijing Road, Guiyang, 550001 Guizhou, ChinaSchool of Forensic Medicine, Guizhou Medical University, 4 Beijing Road, Guiyang, 550001 Guizhou, ChinaSchool of Forensic Medicine, Guizhou Medical University, 4 Beijing Road, Guiyang, 550001 Guizhou, ChinaSchool of Forensic Medicine, Guizhou Medical University, 4 Beijing Road, Guiyang, 550001 Guizhou, ChinaSchool of Forensic Medicine, Guizhou Medical University, 4 Beijing Road, Guiyang, 550001 Guizhou, ChinaSchool of Forensic Medicine, Guizhou Medical University, 4 Beijing Road, Guiyang, 550001 Guizhou, ChinaThis study was aimed at identifying molecular markers associated with the pathogenesis of sudden cardiac death (SCD). It provides a proteomic analysis of human left anterior descending coronary artery from subjects diagnosed with SCD through histological examination and cases of nondisease accidental deaths through autopsy. A total of 2784 proteins were obtained from label-free quantitative proteomic analysis. This included a total of 265 differential proteins which were involved in SCD-related processes, such as inflammation, muscle system process regulation, metal ion transport, and lysosomal pathway. Western blotting was carried out to measure the expressions of cathepsin C (CTSC), focal adhesion kinase (FAK), p-FAK, and proteins related to the p38/MAPK signaling pathway, whereas immunohistochemistry was performed to determine the localization and expression of CTSC, TNF-α, and CD206 in arterial tissues. It was found that CTSC were the most expressed proteins with a significant upward trend in SCD cases. Besides, CTSC regulated macrophage polarization to M1 through the FAK-induced p38/MAPK signaling pathway. This promoted the release of inflammatory factors and eventually increased the inflammatory response. In conclusion, this study implies that CTSC may be one of the key molecular targets for promoting macrophage M1 polarization in SCD, which may provide new therapeutic insights into the treatment of inflammatory diseases.http://dx.doi.org/10.1155/2021/6139732
spellingShingle Jialin Dai
Jiangjin Liu
Qiong Zhang
Yang An
Bing Xia
Changwu Wan
Yuanyuan Zhang
Yanni Yu
Jie Wang
Cathepsin C Is Involved in Macrophage M1 Polarization via p38/MAPK Pathway in Sudden Cardiac Death
Cardiovascular Therapeutics
title Cathepsin C Is Involved in Macrophage M1 Polarization via p38/MAPK Pathway in Sudden Cardiac Death
title_full Cathepsin C Is Involved in Macrophage M1 Polarization via p38/MAPK Pathway in Sudden Cardiac Death
title_fullStr Cathepsin C Is Involved in Macrophage M1 Polarization via p38/MAPK Pathway in Sudden Cardiac Death
title_full_unstemmed Cathepsin C Is Involved in Macrophage M1 Polarization via p38/MAPK Pathway in Sudden Cardiac Death
title_short Cathepsin C Is Involved in Macrophage M1 Polarization via p38/MAPK Pathway in Sudden Cardiac Death
title_sort cathepsin c is involved in macrophage m1 polarization via p38 mapk pathway in sudden cardiac death
url http://dx.doi.org/10.1155/2021/6139732
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