Identification and validation of cholesterol homeostasis and NK cell-associated predictive and therapeutic models for Coronary atherosclerotic heart disease patients with ST-elevated myocardial infarction: Insights from artificial intelligence and multi-omics

OBJECTIVE: Dysregulation of Cholesterol homeostasis(CH) and NK cells proportion can increase risk of ST-Elevated Myocardial Infarction(STEMI) for Coronary atherosclerotic heart disease(CAD) patients. Hence, it is necessary for the investigation of CH and MC in pathogenesis of STEMI for CAD patients, providing additional choice for the prevention of STEMI for CAD patients. METHODS: By combining 5 peripheral blood bulk profiles of CAD patients with STEMI and integrative bioinformatic pipelines, such as ssGSEA, CIBERSORT, WGCNA, machine learning, consensus clustering, we first identified novel CH and NK cell(NCH)-associated molecular subgroup and hub genes for CAD patients with STEMI, and then estimated hub genes predictive performance for STEMI onset among CAD patients. Besides, the biological features of hub gene were estimated both in bulk and single-cell profiles of CAD patients with STEMI, especially in artificial intelligence(AI)-driven virtual cells. Indeed, AI-empowered therapeutic enrichment framework(DrugRefLector) and molecular docking were cross-performed for identification of optimal preventative agents targeting hub genes for CAD patients. Finally, in vitro study confirmed the differentially expressed level of hub genes. RESULTS: Integrated NCH can lead to the molecular stratification for CAD patients with AMI, which provides insights into the patient precision medicine. Besides, NAMPT and CLEC4D can be considered as up-regulated NCH-associated hub gene involved in STEMI pathogenesis of CAD patients with satisfied predictive efficacy, which was mainly distributed at NK cells. Novelty, BRD-K92455082 can be considered as optimal STEMI-preventative agent for the CAD patients by targeting NAMPT and CLEC4D. CONCLUSION: Our study provides integrative evidence suggesting a potential combined role of cholesterol homeostasis and NK cell-associated transcriptional programs of AMI for CAD patients, which offers novel insights into patient precision and personalized medicine.