Identification of immune feature genes and intercellular profiles in diabetic cardiomyopathy

作     者：Ze-Qun Zheng Di-Hui Cai Yong-Fei Song 

作者机构：Ningbo Institute of Innovation for Combined Medicine and EngineeringThe Affiliated Lihuili Hospital of Ningbo UniversityNingbo 315040Zhejiang ProvinceChina Department of CardiologyClinical Research CenterShantou University Medical CollegeShantou 515041Guangdong ProvinceChina 

出 版 物：《World Journal of Diabetes》 (世界糖尿病杂志（英文版）（电子版）)

年 卷 期：2024年第15卷第10期

页      面：2093-2110页

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：Supported by National Natural Science Foundation of China,No.82300347 Natural Science Foundation of Ningbo,No.2021J296 Science Foundation of Lihuili Hospital,No.2022ZD004 

主　　题：Diabetic cardiomyopathy Immune feature genes Proenkephalin Retinol binding protein 7 Immune cell infiltration Intercellular communication 

摘      要：BACKGROUND Diabetic cardiomyopathy(DCM)is a multifaceted cardiovascular disorder in which immune dysregulation plays a pivotal *** immunological molecular mechanisms underlying DCM are poorly *** To examine the immunological molecular mechanisms of DCM and construct diagnostic and prognostic models of DCM based on immune feature genes(IFGs).METHODS Weighted gene co-expression network analysis along with machine learning methods were employed to pinpoint IFGs within bulk RNA sequencing(RNA-seq)***-sample gene set enrichment analysis(ssGSEA)facilitated the analysis of immune cell *** and prognostic models for these IFGs were developed and assessed in a validation *** expression in the DCM cell model was confirmed through real time-quantitative polymerase chain reaction and western blotting ***,single-cell RNA-seq data provided deeper insights into cellular profiles and *** The overlap between 69 differentially expressed genes in the DCM-associated module and 2483 immune genes yielded 7 differentially expressed immune-related *** IFGs showed good diagnostic and prognostic values in the validation cohort:Proenkephalin(Penk)and retinol binding protein 7(Rbp7),which were highly expressed,and glucagon receptor and inhibin subunit alpha,which were expressed at low levels in DCM patients(all area under the curves0.9).SsGSEA revealed that IFG-related immune cell infiltration primarily involved type 2 T helper *** expression of Penk(P0.0001)and Rbp7(P=0.001)was detected in cardiomyocytes and interstitial cells and further confirmed in a DCM cell model in *** events and communication analysis revealed abnormal cellular phenotype transformation and signaling communication in DCM,especially between mesenchymal cells and *** The present study identified Penk and Rbp7 as potential DCM biomarkers,and aberrant mesenchymal-immune cell phenotyp