赵鹏辉,陈露,蔡嘉庚,徐媛,李显龙,祖凌云

• 1:北京大学第三医院心血管内科血管医学研究所血管稳态与重构全国重点实验室国家卫生健康委心血管分子生物学与调节肽重点实验室心血管受体研究北京市重点实验室
• 2:北京大学第三医院基础医学研究中心

摘要(Abstract)：

目的 钙化性主动脉瓣疾病（CAVD）是第三大心血管病，临床确诊常处于晚期阶段，且治疗多依赖瓣膜置换术。本研究旨在探索CAVD的潜在分子机制与药物靶点。方法 本研究收集2022年11月至2023年10月北京大学第三医院人心脏外科术后瓣膜样本（CAVD组、对照组各3例）开展转录组测序并采用R语言进行生信分析。结果 鉴定出506个差异表达基因（上调216个、下调290个）。基因本体论（GO）富集分析表明，B细胞介导的免疫应答等功能显著富集；京都基因和基因组百科全书（KEGG）富集结果显示，硒化合物代谢、甘氨酸/丝氨酸/苏氨酸代谢、细胞外基质-受体相互作用等多条通路显著参与。结合基因表达综合数据库（GEO）数据集交叉验证，发现IBSP等基因在CAVD组表达显著异常，支持其与CAVD密切相关。基于Connectivity Map(CMap)预测，PP-2(SRC抑制剂)与GDC-0941(PI3K抑制剂)与成骨/矿化过程相关，且分子对接结果提示二者均与靶蛋白IBSP结合良好。结论 代谢网络及细胞外基质-受体相互作用可能是CAVD的重要调控通路，IBSP等基因有望作为干预靶点；PP-2与GDC-0941或可分别通过SRC–IBSP轴与PI3K–AKT–RUNX2–IBSP轴调控主动脉瓣的病理性钙化，值得进一步验证。

关键词(KeyWords)： 钙化性主动脉瓣疾病;分子机制;抗钙化靶点;转录组学;生物信息学

Abstract:

Keywords:

基金项目(Foundation): 国家重点研发计划项目(2022YFB3807300)

作者(Author): 赵鹏辉,陈露,蔡嘉庚,徐媛,李显龙,祖凌云

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