昆明医科大学学报2025，Vol.46Issue(12)：9-20,12.DOI:10.12259/j.issn.2095-610X.S20251202
脂代谢相关基因ASP和PPARα在动脉粥样硬化中的作用
Effects of Lipid Metabolism-related Genes ASP and PPARα in Atherosclerosis
摘要
Abstract
Objective To investigate the roles of lipid metabolism-related genes ASP and PPARα in atherosclerosis(AS).Methods Datasets GSE9874,GSE28829,and GSE21545 were retrieved from the GEO database and intersected to identify common differentially expressed genes(DEGs).Gene Ontology(GO)and Kyoto E ncyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed on the DEGs.Protein-protein interaction(PPI)networks were constructed using the String database,and critical genes were screened using Cytoscape software.Additionally,interacting genes of critical genes were identified using the GeneMANIA database,and molecular docking predictions were performed using HDOCK software,with further in vivo experimental validation,Atherosclerosis model was established in C57BL/6J mice.Oil Red O staining was used to observe plaque deposition areas in the whole aorta and aortic sinuses of each group.Hematoxylin-eosin(HE)staining was performed to observe pathological changes in aortic sinus tissues.ELISA was used to detect serum lipid levels and expression levels of PCSK9,ASP,and PPARα.Reverse transcription quantitative PCR(RT-qPCR)and Western blotting(WB)were used to detect mRNA and protein expression levels of ASP and PPARα in aortic tissues.Co-immunoprecipitation(CO-IP)analysis was performed to investigate the interaction between ASP and PPARα proteins.Results A total of 35 differentially expressed genes in AS were identified,primarily enriched in cholesterol transfer activity,phosphatidylcholine transport activity,ABC transporters,and autophagy pathways.PPI and Cytoscape analyses identified ASP as a critical gene.Through the GeneMANIA database,PPARα was identified as an interacting gene of ASP.Molecular docking predictions revealed a strong interaction between the two proteins forming a stable structure.In vivo experiments showed that compared with the normal diet group,the high-fat diet and atherosclerosis groups exhibited varying degrees of damage to aortic morphology with increased plaque area;serum lipid levels were significantly elevated and ASP mRNA and protein levels in aortic tissues were significantly increased(P<0.05),while PPARα levels showed the opposite pattern.Compared with the high-fat diet group,these indicators in the atherosclerosis group showed statistically significant differences(P<0.05).CO-IP analysis confirmed the interaction between ASP and PPARα.In ASP-knockdown mice,atherosclerotic plaques and serum lipid levels decreased while PPARα expression levels increased(P<0.05).Conclusion ASP and PPARα participate in the development of atherosclerosis and may be closely related to lipid metabolism.关键词
动脉粥样硬化/脂代谢/促酰化蛋白/过氧化物酶增殖核受体αKey words
Atherosclerosis/Lipid metabolism/Acylation stimulating protein/Peroxisome proliferator-activated receptor α分类
医药卫生引用本文复制引用
WANG Yating,XIE Wei,GUAN Yaling,ABULAITI Dilihumar,YE Meng,JIA Taotao,GAO Ying..脂代谢相关基因ASP和PPARα在动脉粥样硬化中的作用[J].昆明医科大学学报,2025,46(12):9-20,12.基金项目
新疆维吾尔自治区天山英才科技创新领军人才项目(2022TSYCLJ0023) （2022TSYCLJ0023）
新疆维吾尔自治区自然科学基金(2023D01D13) （2023D01D13）
新疆维吾尔自治区重点研发计划项目(2024B03036-1) （2024B03036-1）
