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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Bibliographic Details
Published in:Cardiovascular therapeutics 2021-10, Vol.2021, p.6139732-12
Main Authors: Dai, Jialin, Liu, Jiangjin, Zhang, Qiong, An, Yang, Xia, Bing, Wan, Changwu, Zhang, Yuanyuan, Yu, Yanni, Wang, Jie
Format: Article
Language:English
Subjects:
Atherosclerosis
Autopsies
Bioinformatics
Cardiac arrest
Cardiovascular disease
Cathepsin C - metabolism
Cathepsins
Chromatography
Coronary vessels
Death, Sudden, Cardiac - etiology
Health aspects
Heart
Humans
Immunohistochemistry
Inflammation
Macrophages
Mass spectrometry
p38 Mitogen-Activated Protein Kinases
Pathogenesis
Pathology
Peptides
Proteins
Proteomics
Scientific imaging
Search engines
Software
Values
Veins & arteries
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Summary: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.
ISSN:1755-5914
1755-5922
DOI:10.1155/2021/6139732