ABCA1来源的环状RNA调控胆固醇稳态影响冠脉病变程度  

ABCA1-derived circRNA Regulates Cholesterol Homeostasis and Affects the Severity of Coronary Artery Lesions

作　　者：王蓉莉 汪静 丁虎 Wang Rongli;Wang Jing;Ding Hu(Department of Cardiology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China)

机构地区：[1]华中科技大学同济医学院附属同济医院心血管内科,武汉430030

出　　处：《华中科技大学学报(医学版)》2025年第2期143-150,共8页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：十四五国家重点研发计划项目(No.2021YFC2500604)。

摘　　要：目的探讨ABCA1基因来源的环状RNA(circABCA1)在调节胆固醇稳态中的作用及其与冠心病的临床相关性。方法通过RT-PCR和免疫蛋白印记法评估巨噬细胞中circABCA1对ABCA1基因表达的影响,通过油红O染色等检测细胞内脂质沉积情况。检测冠心病人群的外周血单个核细胞(PBMCs)中circABCA1的表达水平,探究其与冠心病患者血脂水平、冠脉病变程度的相关性,利用多因素Logistic回归分析评估circABCA1是否为冠心病的独立危险因素。结果过表达circABCA1抑制THP-1细胞ABCA1表达,显著升高总胆固醇水平、促进脂质沉积、减少胆固醇流出;在冠心病患者PBMCs中circABCA1的表达水平与患者血浆总胆固醇水平(r=0.3545,P<0.01)、Gensini评分(r=0.3690,P<0.01)呈正相关,circABCA1是预测冠心病发病风险的生物标志物(P<0.01)。结论circABCA1通过抑制ABCAl影响PBMCs中胆固醇稳态,增加冠脉病变程度,,提示circABCA1为功能性RNA,是冠心病防治潜在干预靶点。Objective To explore the role of circular RNA derived from the ABCA1 gene(circABCA1)in regulating cholesterol homeostasis and its clinical relevance to coronary artery diseases(CAD).Methods Real-time PCR and Western blot were used to assess the expression of ABCA1.Intracellular lipid deposition was detected by oil red O staining.The expression level of circABCAl was detected in PBMCs collected from CAD patients.Spearman correlation analysis was used to explore the correlation between circABCAl and lipid levels as well as the degree of coronary artery lesions.Multivariate logistic regression analysis was used to evaluate whether circABCAl is an independent risk factor for coronary heart disease.Results ABCAl expression was inhibited,total cholesterol levels and lipid deposition significantly elevated in cells after overexpression of circABCAl.In patients with coronary artery disease,the expression level of circABCAl was positively correlated with lipid levels(r=0.3545,P<0.01)and Gensini score(r=0.3690,P<0.01).The risk of coronary heart disease was increased after upregulation of circABCAl.Conclusion circABCAl promotes intracellular lipid deposition by inhibiting ABCA1 expression and shows a significant positive correlation with the degree of coronary artery lesions,suggesting that circABCA1 is a functional RNA and a potential intervention target for the prevention and treatment of CAD.

关 键 词：环状RNA ABCAl 胆固醇稳态 冠心病 生物标志物 

分 类 号：R541.4[医药卫生—心血管疾病]