Deng Ting, Liu Yongguang, Gael Akindavyi, Fu Xiaohua, Deng Xiaofang, Liu Yunfeng, Wu Yizhang, Wu Yingzhi, Wang Huimin, Deng Yuying, Lai Jun, Fu Qiang
Department of Cardiovascular Disease, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Department of Cardiology, Laboratory of Heart Center, Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Front Physiol. 2022 Jul 15;13:862732. doi: 10.3389/fphys.2022.862732. eCollection 2022.
Aortic dissection refers to the separation of aortic media and extension along the long axis to form the true and false chambers of the aortic wall. 65-70% of the patients died of cardiac tamponade, arrhythmia, dissection rupture, etc. At present, echocardiography, computed tomography angiography (CTA), etc. are the main diagnosis tools for aortic dissection. To date, there is no rapid serum molecular marker that can be used for differential diagnosis and risk assessment. To screen serum molecular markers systematically amid aortic dissection and acute coronary syndrome and to preliminarily identify the pathogenesis of acute aortic dissection. Related disputes cases of all hospitals were statistically analyzed for the AAD medical disputes ratio, early death ratio and misdiagnosis ratio from the database of Guangdong Province Medical Disputes Coordination Committee from 2013 to 2017. Serum and Aortic tissues samples were respectively quantified by iTRAQ and label-free analysis, further validated by ELISA and protein verified by immunofluorescence and Western blot from AAD and control patients enrolled from the Zhujiang Hospital of Southern Medical University and Guangdong Province people's Hospital from 2016 to 2018. AAD cases ratio accounted for 15.29% in all 150 cardiovascular disputes, 59.26% in all cardiovascular death less than 24 h, and 88.89% in the patients who remained undiagnosed at the time of death, 84 proteins (66 and 18 upregulated and downregulated, respectively) were identified by iTRAQ and 16 proteins (9 and 7 upregulated and downregulated, respectively) by Label-free. Nine proteins (Lumican, FGL1, PI16, MMP9, FBN1, MMP2, VWF, MMRN1, and PF4) related to the pathogenesis of aortic dissection were identified by David /Ease and String techniques as candidate biomarkers for verification test. Four proteins (Lumican, FGL1, PI16, and MMP9) were found to be statistically different after ELISA verification. The expression of FGL1, PI16, and MMP9 proteins was pathologically significantly increased except for Lumican. Histologically, TGF-β1, α-SMA, and Collagen1 were also significantly higher in the aortic group. Lumican, FGL1, PI16, and MMP9 may be potential biomarkers in AAD patients, and the Lumican-mediated TGF-β1 pathway is likely to be involved in the pathogenesis of aortic dissection.
主动脉夹层是指主动脉中膜分离并沿长轴延伸，形成主动脉壁的真腔和假腔。65% - 70%的患者死于心包填塞、心律失常、夹层破裂等。目前，超声心动图、计算机断层扫描血管造影（CTA）等是主动脉夹层的主要诊断工具。迄今为止，尚无可用于鉴别诊断和风险评估的快速血清分子标志物。旨在系统筛选主动脉夹层和急性冠脉综合征中的血清分子标志物，并初步明确急性主动脉夹层的发病机制。对2013年至2017年广东省医疗纠纷协调委员会数据库中各医院的相关纠纷病例进行统计分析，得出主动脉夹层医疗纠纷发生率、早期死亡率和误诊率。分别采用iTRAQ和无标记分析对血清和主动脉组织样本进行定量，通过酶联免疫吸附测定（ELISA）进一步验证，并采用免疫荧光和蛋白质免疫印迹法对2016年至2018年从南方医科大学珠江医院和广东省人民医院招募的主动脉夹层患者及对照患者的蛋白质进行验证。在所有150例心血管纠纷中，主动脉夹层病例占15.29%；在所有心血管疾病24小时内死亡病例中，占59.26%；在死亡时仍未确诊的患者中，占88.89%。通过iTRAQ鉴定出84种蛋白质（分别有66种上调和18种下调），通过无标记分析鉴定出16种蛋白质（分别有9种上调和7种下调）。通过David /Ease和String技术鉴定出9种与主动脉夹层发病机制相关的蛋白质（核纤层蛋白、FGL1、PI16、基质金属蛋白酶9、原纤维蛋白1、基质金属蛋白酶2、血管性血友病因子、多配体蛋白聚糖1和血小板因子4）作为验证试验的候选生物标志物。ELISA验证后发现4种蛋白质（核纤层蛋白、FGL1、PI16和基质金属蛋白酶9）存在统计学差异。除核纤层蛋白外，FGL1、PI16和基质金属蛋白酶9蛋白的表达在病理上显著增加。组织学上，主动脉组中转化生长因子-β1、α - 平滑肌肌动蛋白和胶原蛋白1也显著升高。核纤层蛋白、FGL1、PI16和基质金属蛋白酶9可能是主动脉夹层患者的潜在生物标志物，核纤层蛋白介导的转化生长因子-β1途径可能参与主动脉夹层的发病机制。
