Ran Haoyu, Li Changying, Rizvi Syed M Musa, Zhou Ruiqin, Kong Lingwen, Shuangling Sun, Shao Yue, Wu Kejia, Duan Changzhu, Luo Jun, Shi Haoming, Wu Qingchen, Zhang Cheng
Department of Cardiothoracic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Cardiothoracic Surgery, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, China.
Sci Rep. 2024 Dec 30;14(1):32062. doi: 10.1038/s41598-024-83611-0.
Plasma secretory proteins are associated with various diseases, including aortic dissection (AD). However, current research on the correlation between AD and plasma protein levels is scarce or lacks specificity. This study aimed to explore plasma secretory proteins as potential biomarkers for AD. Through genome-wide association studies, expression quantitative trait locus (eQTL) analysis, and human plasma protein profiling, we identified DBNL, NPC2, SUMF2, and TFPI as high-risk genes and CCN3, PRKCSH, TEX264, and TGFBR3 as low-risk genes for AD. Further cell localization and differential expression analysis of these eight genes were conducted using single-cell data. We also examined their expression in three Gene Expression Omnibus datasets, measured their mRNA levels in AD versus normal tissues using qPCR, and assessed their protein levels in patients' blood versus healthy individuals using enzyme-linked immunosorbent assay. Our findings suggest that CCN3, consistently downregulated in both mRNA and plasma levels during AD, may have a protective role. Initial enrichment analyses of differentially expressed CCN3 cells suggested their involvement in focal adhesion, actin cytoskeleton regulation, and the PI3K-Akt signaling pathway.
血浆分泌蛋白与包括主动脉夹层（AD）在内的多种疾病相关。然而，目前关于AD与血浆蛋白水平之间相关性的研究较少或缺乏特异性。本研究旨在探索血浆分泌蛋白作为AD潜在生物标志物的可能性。通过全基因组关联研究、表达定量性状位点（eQTL）分析和人类血浆蛋白谱分析，我们确定DBNL、NPC2、SUMF2和TFPI为AD的高风险基因，CCN3、PRKCSH、TEX264和TGFBR3为低风险基因。利用单细胞数据对这八个基因进行了进一步的细胞定位和差异表达分析。我们还在三个基因表达综合数据库中检测了它们的表达情况，使用qPCR测量了它们在AD组织与正常组织中的mRNA水平，并使用酶联免疫吸附测定法评估了它们在患者血液与健康个体中的蛋白水平。我们的研究结果表明，CCN3在AD期间mRNA和血浆水平均持续下调，可能具有保护作用。对差异表达的CCN3细胞进行的初步富集分析表明，它们参与了粘着斑、肌动蛋白细胞骨架调节和PI3K-Akt信号通路。
