Uncovering Hippo pathway-related biomarkers in acute myocardial infarction via scRNA-seq binding transcriptomics

被引:0
作者
Li, Xingda [1 ,2 ,3 ,4 ]
He, Xueqi [3 ,4 ]
Zhang, Yu [3 ,4 ]
Hao, Xinyuan [3 ,4 ]
Xiong, Anqi [6 ]
Huang, Jiayu [6 ]
Jiang, Biying [6 ]
Tong, Zaiyu [6 ]
Huang, Haiyan [5 ]
Yi, Lian [5 ]
Chen, Wenjia [6 ]
机构
[1] Harbin Med Univ, Natl Key Lab Frigid Zone Cardiovasc Dis, State Prov Key Labs Biomed Pharmaceut China, Dept Pharmacol,Key Lab Cardiovasc Res,Minist Educ, Harbin 150086, Heilongjiang, Peoples R China
[2] Harbin Med Univ, Coll Pharm, Int Cooperat Base Major Cardiovasc Dis Cold Reg, Harbin 150086, Heilongjiang, Peoples R China
[3] Harbin Med Univ, Dept Pharm, Affiliated Hosp 2, Harbin 150086, Peoples R China
[4] Harbin Med Univ, Dept Pharmacol, Key Lab Cardiovasc Res, Minist Educ,Coll Pharm, Harbin 150086, Peoples R China
[5] Harbin Med Univ, Dept Neurol, Affiliated Hosp 1, Harbin 150001, Peoples R China
[6] Harbin Med Univ, Dept Cardiol, Affiliated Hosp 1, 23 YouZheng St, Harbin 150001, Heilongjiang, Peoples R China
来源
SCIENTIFIC REPORTS | 2025年 / 15卷 / 01期
基金
中国国家自然科学基金; 中国博士后科学基金;
关键词
Acute myocardial infarction; Hippo signaling pathway; Biomarkers; Immune infiltration; Endothelial cell; Macrophage; HEPATOCELLULAR-CARCINOMA; HEART-FAILURE; PROTEIN; EXPRESSION; SURVIVAL; NAD(+); KEGG;
D O I
10.1038/s41598-025-94820-6
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
This study investigated Hippo signaling pathway-related biomarkers in acute myocardial infarction (AMI). First, differentially expressed genes (DEGs) between AMI patients and controls were identified. Consensus clustering then classified AMI subtypes, followed by subtype-specific DEG screening. Candidate genes were derived from intersecting initial DEGs with subtype-associated DEGs. Three machine-learning algorithms prioritized five biomarkers (NAMPT, CXCL1, CREM, GIMAP6, and GIMAP7), validated through multi-dataset analyses and cellular expression profiling. qRT-PCR and Western blot confirmed differential expression patterns between AMI and controls across experimental models. Notably, NAMPT, CXCL1, and GIMAP6 exhibited cell-type-specific expression in endothelial cells and macrophages. We further predicted 179 potential therapeutic agents targeting these biomarkers. Niclosamide and eugenol were observed to mitigate hypoxia-induced injury in neonatal mouse ventricular cardiomyocytes. In vivo experiments demonstrated upregulated NAMPT/CXCL1 and downregulated GIMAP6/GIMAP7 in AMI myocardial tissues, with significant NAMPT protein elevation. These biomarkers show clinical diagnostic potential and provide mechanistic insights into AMI pathogenesis.
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页数:20
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