The Association and Pathogenesis of SERPINA3 in Coronary Artery Disease.
The Association and Pathogenesis of SERPINA3 in Coronary Artery Disease.
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SERPINA3与冠心病的关联及发病机制
DOI：
10.3389/fcvm.2021.756889
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发表时间：
2021
影响因子：
3.6
通讯作者：
Peng W
中科院分区：
文献类型：
--
作者：
Li B;Lei Z;Wu Y;Li B;Zhai M;Zhong Y;Ju P;Kou W;Shi Y;Zhang X;Peng W
背景：丝氨酸蛋白酶抑制剂A3 （SERPINA3）在许多人类疾病的发病机制中已被发现，但SERPINA3在冠状动脉疾病（CAD）中的作用却知之甚少。因此，我们的目的是确定其与CAD的关系及其在动脉粥样硬化发病中的作用。方法：将86例冠心病患者与64例非冠心病患者进行比较。ELISA法检测血浆SERPINA3水平。采用Logistic回归分析和受试者工作特征（ROC）分析来说明血浆SERPINA3水平与CAD之间的关系。体外采用实时荧光定量PCR （RT-PCR）和免疫荧光染色法检测SERPINA3在动脉粥样硬化斑块及其组成细胞中的表达。然后用siRNA转染大鼠主动脉平滑肌细胞（RASMCs），敲低SERPINA3的表达，用SERPINA3蛋白刺激人脐静脉内皮细胞（HUVECs）。用EdU法和划痕法测定细胞的增殖和迁移能力。western blot和RT-PCR检测细胞信号通路。结果：冠心病患者血浆SERPINA3水平[104.4(54.5-259.2)μg/mL]高于非冠心病患者[65.3(47.5-137.3)μg/mL] （P = 0.004）。完全调整后，血浆SERPINA3的对数转换和分位数水平与冠心病有显著相关性。但其诊断价值较低，ROC曲线下面积为0.64 （95% CI: 0.55 ~ 0.73）。分泌SERPINA3可能增加huvec中炎症因子的表达。与内皮细胞和炎症细胞相比，血管平滑肌细胞在主动脉中SERPINA3表达最高。在RASMCs中，SERPINA3基因的敲低会减弱其增殖和迁移。当SERPINA3被敲低时，磷酸化的i - κ b α及其下游通路受到抑制。结论：血浆SERPINA3水平升高与冠心病相关。SERPINA3可以增加huvec中炎症因子的表达。通过NF-κB信号通路调节VSMCs的增殖、迁移和炎症因子的释放。由此可见，SERPINA3在动脉粥样硬化的发病机制中发挥了重要作用。
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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影响因子：
20.1
作者：
Kobiyama K;Ley K
通讯作者：
Ley K
影响因子：
20.1
作者：
Pi X;Xie L;Patterson C
通讯作者：
Patterson C
影响因子：
5.5
作者：
Turnier, Jessica L.;Brunner, Hermine I.;Aronow, Bruce
通讯作者：
Aronow, Bruce
影响因子：
5.3
作者：
Li, Hailing;Peng, Wenhui;Xu, Yawei
通讯作者：
Xu, Yawei
血浆卡利他汀减少与冠状动脉疾病的严重程度相关，卡利他汀治疗可减轻小鼠动脉粥样硬化斑块的形成。
影响因子：
5.4
作者：
Yao, Yuyu;Li, Bing;Chao, Julie
通讯作者：
Chao, Julie