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The Association and Pathogenesis of SERPINA3 in Coronary Artery Disease

Background: Serine proteinase inhibitor A3 (SERPINA3) has been discovered in the pathogenesis of many human diseases, but little is known about the role of SERPINA3 in coronary artery disease (CAD). Therefore, we aim to determine its relationship with CAD and its function in the pathogenesis of athe...

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Autores principales: Li, Bo, Lei, Zhijun, Wu, You, Li, Bingyu, Zhai, Ming, Zhong, Yuan, Ju, Peinan, Kou, Wenxin, Shi, Yefei, Zhang, Xianling, Peng, Wenhui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8692672/
https://www.ncbi.nlm.nih.gov/pubmed/34957248
http://dx.doi.org/10.3389/fcvm.2021.756889
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author Li, Bo
Lei, Zhijun
Wu, You
Li, Bingyu
Zhai, Ming
Zhong, Yuan
Ju, Peinan
Kou, Wenxin
Shi, Yefei
Zhang, Xianling
Peng, Wenhui
author_facet Li, Bo
Lei, Zhijun
Wu, You
Li, Bingyu
Zhai, Ming
Zhong, Yuan
Ju, Peinan
Kou, Wenxin
Shi, Yefei
Zhang, Xianling
Peng, Wenhui
author_sort Li, Bo
collection PubMed
description Background: Serine proteinase inhibitor A3 (SERPINA3) has been discovered in the pathogenesis of many human diseases, but little is known about the role of SERPINA3 in coronary artery disease (CAD). Therefore, we aim to determine its relationship with CAD and its function in the pathogenesis of atherosclerosis. Methods: In total 86 patients with CAD and 64 patients with non-CAD were compared. The plasma SERPINA3 levels were measured using ELISA. Logistic regression analysis and receiver-operating characteristic (ROC) analysis were performed to illustrate the association between plasma SERPINA3 levels and CAD. In vitro, real-time PCR (RT-PCR) and immunofluorescence staining were used to determine the expression of SERPINA3 in atherosclerotic plaques and their component cells. Then rat aortic smooth muscle cells (RASMCs) were transfected with siRNA to knock down the expression of SERPINA3 and human umbilical vein endothelial cells (HUVECs) were stimulated by SERPINA3 protein. EdU assay and scratch assay were used for assessing the capability of proliferation and migration. The cell signaling pathway was evaluated by western blot and RT-PCR. Results: Patients with CAD [104.4(54.5–259.2) μg/mL] had higher levels of plasma SERPINA3 than non-CAD [65.3(47.5–137.3) μg/mL] (P = 0.004). After being fully adjusted, both log-transformed and tertiles of plasma SERPINA3 levels were significantly associated with CAD. While its diagnostic value was relatively low since the area under the ROC curve was 0.64 (95% CI: 0.55–0.73). Secreted SERPINA3 might increase the expression of inflammatory factors in HUVECs. Vascular smooth muscle cells had the highest SERPINA3 expression among the aorta compared to endothelial cells and inflammatory cells. The knockdown of SERPINA3 in RASMCs attenuated its proliferation and migration. The phosphorylated IκBα and its downstream pathway were inhibited when SERPINA3 was knocked down. Conclusions: Elevated plasma SERPINA3 levels were associated with CAD. SERPINA3 can increase inflammatory factors expression in HUVECs. It can regulate VSMCs proliferation, migration, and releasing of inflammatory factors through the NF-κB signaling pathway. Thus, SERPINA3 played a significant role in the pathogenesis of atherosclerosis.
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spelling pubmed-86926722021-12-23 The Association and Pathogenesis of SERPINA3 in Coronary Artery Disease Li, Bo Lei, Zhijun Wu, You Li, Bingyu Zhai, Ming Zhong, Yuan Ju, Peinan Kou, Wenxin Shi, Yefei Zhang, Xianling Peng, Wenhui Front Cardiovasc Med Cardiovascular Medicine Background: Serine proteinase inhibitor A3 (SERPINA3) has been discovered in the pathogenesis of many human diseases, but little is known about the role of SERPINA3 in coronary artery disease (CAD). Therefore, we aim to determine its relationship with CAD and its function in the pathogenesis of atherosclerosis. Methods: In total 86 patients with CAD and 64 patients with non-CAD were compared. The plasma SERPINA3 levels were measured using ELISA. Logistic regression analysis and receiver-operating characteristic (ROC) analysis were performed to illustrate the association between plasma SERPINA3 levels and CAD. In vitro, real-time PCR (RT-PCR) and immunofluorescence staining were used to determine the expression of SERPINA3 in atherosclerotic plaques and their component cells. Then rat aortic smooth muscle cells (RASMCs) were transfected with siRNA to knock down the expression of SERPINA3 and human umbilical vein endothelial cells (HUVECs) were stimulated by SERPINA3 protein. EdU assay and scratch assay were used for assessing the capability of proliferation and migration. The cell signaling pathway was evaluated by western blot and RT-PCR. Results: Patients with CAD [104.4(54.5–259.2) μg/mL] had higher levels of plasma SERPINA3 than non-CAD [65.3(47.5–137.3) μg/mL] (P = 0.004). After being fully adjusted, both log-transformed and tertiles of plasma SERPINA3 levels were significantly associated with CAD. While its diagnostic value was relatively low since the area under the ROC curve was 0.64 (95% CI: 0.55–0.73). Secreted SERPINA3 might increase the expression of inflammatory factors in HUVECs. Vascular smooth muscle cells had the highest SERPINA3 expression among the aorta compared to endothelial cells and inflammatory cells. The knockdown of SERPINA3 in RASMCs attenuated its proliferation and migration. The phosphorylated IκBα and its downstream pathway were inhibited when SERPINA3 was knocked down. Conclusions: Elevated plasma SERPINA3 levels were associated with CAD. SERPINA3 can increase inflammatory factors expression in HUVECs. It can regulate VSMCs proliferation, migration, and releasing of inflammatory factors through the NF-κB signaling pathway. Thus, SERPINA3 played a significant role in the pathogenesis of atherosclerosis. Frontiers Media S.A. 2021-12-08 /pmc/articles/PMC8692672/ /pubmed/34957248 http://dx.doi.org/10.3389/fcvm.2021.756889 Text en Copyright © 2021 Li, Lei, Wu, Li, Zhai, Zhong, Ju, Kou, Shi, Zhang and Peng. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Li, Bo
Lei, Zhijun
Wu, You
Li, Bingyu
Zhai, Ming
Zhong, Yuan
Ju, Peinan
Kou, Wenxin
Shi, Yefei
Zhang, Xianling
Peng, Wenhui
The Association and Pathogenesis of SERPINA3 in Coronary Artery Disease
title The Association and Pathogenesis of SERPINA3 in Coronary Artery Disease
title_full The Association and Pathogenesis of SERPINA3 in Coronary Artery Disease
title_fullStr The Association and Pathogenesis of SERPINA3 in Coronary Artery Disease
title_full_unstemmed The Association and Pathogenesis of SERPINA3 in Coronary Artery Disease
title_short The Association and Pathogenesis of SERPINA3 in Coronary Artery Disease
title_sort association and pathogenesis of serpina3 in coronary artery disease
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8692672/
https://www.ncbi.nlm.nih.gov/pubmed/34957248
http://dx.doi.org/10.3389/fcvm.2021.756889
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