基于蛋白质组学的难治性高血压潜在生物标志物的筛选  

Discovery of potential biomarkers for refractory hypertension based on proteomics

作　　者：王昱琪 王姗姗[2] 郇家铭 李运伦 杨雯晴[2] WANG Yuqi;WANG Shanshan;HUAN Jiaming;LI Yunlun;YANG Wenqing(First Clinical Medicine School,Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong,China;Innovation Research Institute,Shandong University of Traditional Chinese Medicine,Jinan 250300,Shandong,China;The Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong,China)

机构地区：[1]山东中医药大学第一临床医学院,山东济南250014 [2]山东中医药大学创新研究院,山东济南250300 [3]山东中医药大学附属医院,山东济南250014

出　　处：《现代中西医结合杂志》2024年第10期1356-1363,共8页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：山东省自然科学基金重点项目(ZR2020KH034);中国博士后科学基金第73批面上资助项目(2023M732139)。

摘　　要：目的 基于蛋白质组学和复杂网络分析挖掘难治性高血压的潜在生物标志物,探索其关键生物通路。方法 招募2022年1—12月于山东中医药大学附属医院、济南市第五人民医院住院治疗的10例难治性高血压患者作为高血压组,另外招募同时期10例健康人作为健康组。运用蛋白质组学技术分析2组受试者的血液样本,筛选难治性高血压的临床标志物,并结合加权基因共表达网络分析(WGCNA)各个标志物的潜在临床价值。结果 蛋白质组学分析发现,高血压组中共鉴定出60个差异蛋白,主要富集在磷脂酰肌醇3-激酶(PI3K)/蛋白激酶(Akt)和缺氧诱导因子-1(HIF-1)等关键信号传导通路上;蛋白互作结果分析发现,COL6A3、CSF1R、HSPG2、ITGA2、PDGFB、THBS1和vWF是参与难治性高血压发生发展的标志物,这些指标可以通过调节炎症反应、氧化应激、细胞自噬等参与难治性高血压发生发展的病理生理过程。结论 难治性高血压的发病和转归与PI3K/Akt和HIF-1通路中的潜在标志物密切相关,并诱导下游炎症反应,出现COL6A3、CSF1R、HSPG2、ITGA2、PDGFB、THBS1、vWF 7个异常表达的蛋白,这些发现为难治性高血压的诊断和治疗提供了潜在的蛋白靶点。Objective It is to explore the potential biomarkers and key biological pathways of resistant hypertension based on proteomics and complex network analysis.Methods Ten patients with refractory hypertension who were hospitalized in the Affiliated Hospital of Shandong University of Traditional Chinese Medicine and Jinan Fifth People’s Hospital from January to December in 2022 were recruited as the hypertension group,and another 10 healthy individuals were recruited in the same period as the healthy group.The blood samples of subjects of the two groups were analyzed by proteomics technology to screen the clinical markers of resistant hypertension,and their potential clinical values were analyzed by proteomics technology combined with weighted gene co-expression network analysis(WGCNA).Results Proteomic analysis found that 60 differentially expressed proteins were totally identified in the hypertension group,which were mainly enriched in key signal transduction pathways such as phosphatidylinositol 3-kinase(PI3K)/protein kinase(Akt)and hypoxia inducible factor-1(HIF-1).Protein interaction analysis showed that COL6A3,CSF1R,HSPG2,ITGA2,PDGFB,THBS1 and vWF were the markers involved in the development of resistant hypertension,and they could participate in the pathophysiological process of the development of hypertension through the functional regulation of inflammation,oxidative stress,cell autophagy and other aspects.Conclusion The pathogenesis and outcome of refractory hypertension are closely related to the potential markers in PI3K/Akt and HIF-1 pathway,and induce the downstream inflammatory response.The abnormal expressions of 7 proteins,such as COL6A3,HSPG2 and vWF,can be used as biomarkers for early diagnosis of refractory hypertension and target organ damage.

关 键 词：难治性高血压 蛋白质组学 磷脂酰肌醇3-激酶 蛋白激酶 缺氧诱导因子-1 加权基因共表达网络分析 

分 类 号：R544.1[医药卫生—心血管疾病]