Cargando…
Role of mitochondrial metabolic disorder and immune infiltration in diabetic cardiomyopathy: new insights from bioinformatics analysis
BACKGROUND: Diabetic cardiomyopathy (DCM) is one of the common cardiovascular complications of diabetes and a leading cause of death in diabetic patients. Mitochondrial metabolism and immune-inflammation are key for DCM pathogenesis, but their crosstalk in DCM remains an open issue. This study explo...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9893675/ https://www.ncbi.nlm.nih.gov/pubmed/36726122 http://dx.doi.org/10.1186/s12967-023-03928-8 |
_version_ | 1784881576631336960 |
---|---|
author | Peng, Cheng Zhang, Yanxiu Lang, Xueyan Zhang, Yao |
author_facet | Peng, Cheng Zhang, Yanxiu Lang, Xueyan Zhang, Yao |
author_sort | Peng, Cheng |
collection | PubMed |
description | BACKGROUND: Diabetic cardiomyopathy (DCM) is one of the common cardiovascular complications of diabetes and a leading cause of death in diabetic patients. Mitochondrial metabolism and immune-inflammation are key for DCM pathogenesis, but their crosstalk in DCM remains an open issue. This study explored the separate roles of mitochondrial metabolism and immune microenvironment and their crosstalk in DCM with bioinformatics. METHODS: DCM chip data (GSE4745, GSE5606, and GSE6880) were obtained from NCBI GEO, while mitochondrial gene data were downloaded from MitoCarta3.0 database. Differentially expressed genes (DEGs) were screened by GEO2R and processed for GSEA, GO and KEGG pathway analyses. Mitochondria-related DEGs (MitoDEGs) were obtained. A PPI network was constructed, and the hub MitoDEGs closely linked to DCM or heart failure were identified with CytoHubba, MCODE and CTD scores. Transcription factors and target miRNAs of the hub MitoDEGs were predicted with Cytoscape and miRWalk database, respectively, and a regulatory network was established. The immune infiltration pattern in DCM was analyzed with ImmuCellAI, while the relationship between MitoDEGs and immune infiltration abundance was investigated using Spearman method. A rat model of DCM was established to validate the expression of hub MitoDEGs and their relationship with cardiac function. RESULTS: MitoDEGs in DCM were significantly enriched in pathways involved in mitochondrial metabolism, immunoregulation, and collagen synthesis. Nine hub MitoDEGs closely linked to DCM or heart failure were obtained. Immune analysis revealed significantly increased infiltration of B cells while decreased infiltration of DCs in immune microenvironment of DCM. Spearman analysis demonstrated that the hub MitoDEGs were positively associated with the infiltration of pro-inflammatory immune cells, but negatively associated with the infiltration of anti-inflammatory or regulatory immune cells. In the animal experiment, 4 hub MitoDEGs (Pdk4, Hmgcs2, Decr1, and Ivd) showed an expression trend consistent with bioinformatics analysis result. Additionally, the up-regulation of Pdk4, Hmgcs2, Decr1 and the down-regulation of Ivd were distinctly linked to reduced cardiac function. CONCLUSIONS: This study unraveled the interaction between mitochondrial metabolism and immune microenvironment in DCM, providing new insights into the research on potential pathogenesis of DCM and the exploration of novel targets for medical interventions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-023-03928-8. |
format | Online Article Text |
id | pubmed-9893675 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-98936752023-02-03 Role of mitochondrial metabolic disorder and immune infiltration in diabetic cardiomyopathy: new insights from bioinformatics analysis Peng, Cheng Zhang, Yanxiu Lang, Xueyan Zhang, Yao J Transl Med Research BACKGROUND: Diabetic cardiomyopathy (DCM) is one of the common cardiovascular complications of diabetes and a leading cause of death in diabetic patients. Mitochondrial metabolism and immune-inflammation are key for DCM pathogenesis, but their crosstalk in DCM remains an open issue. This study explored the separate roles of mitochondrial metabolism and immune microenvironment and their crosstalk in DCM with bioinformatics. METHODS: DCM chip data (GSE4745, GSE5606, and GSE6880) were obtained from NCBI GEO, while mitochondrial gene data were downloaded from MitoCarta3.0 database. Differentially expressed genes (DEGs) were screened by GEO2R and processed for GSEA, GO and KEGG pathway analyses. Mitochondria-related DEGs (MitoDEGs) were obtained. A PPI network was constructed, and the hub MitoDEGs closely linked to DCM or heart failure were identified with CytoHubba, MCODE and CTD scores. Transcription factors and target miRNAs of the hub MitoDEGs were predicted with Cytoscape and miRWalk database, respectively, and a regulatory network was established. The immune infiltration pattern in DCM was analyzed with ImmuCellAI, while the relationship between MitoDEGs and immune infiltration abundance was investigated using Spearman method. A rat model of DCM was established to validate the expression of hub MitoDEGs and their relationship with cardiac function. RESULTS: MitoDEGs in DCM were significantly enriched in pathways involved in mitochondrial metabolism, immunoregulation, and collagen synthesis. Nine hub MitoDEGs closely linked to DCM or heart failure were obtained. Immune analysis revealed significantly increased infiltration of B cells while decreased infiltration of DCs in immune microenvironment of DCM. Spearman analysis demonstrated that the hub MitoDEGs were positively associated with the infiltration of pro-inflammatory immune cells, but negatively associated with the infiltration of anti-inflammatory or regulatory immune cells. In the animal experiment, 4 hub MitoDEGs (Pdk4, Hmgcs2, Decr1, and Ivd) showed an expression trend consistent with bioinformatics analysis result. Additionally, the up-regulation of Pdk4, Hmgcs2, Decr1 and the down-regulation of Ivd were distinctly linked to reduced cardiac function. CONCLUSIONS: This study unraveled the interaction between mitochondrial metabolism and immune microenvironment in DCM, providing new insights into the research on potential pathogenesis of DCM and the exploration of novel targets for medical interventions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-023-03928-8. BioMed Central 2023-02-01 /pmc/articles/PMC9893675/ /pubmed/36726122 http://dx.doi.org/10.1186/s12967-023-03928-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Peng, Cheng Zhang, Yanxiu Lang, Xueyan Zhang, Yao Role of mitochondrial metabolic disorder and immune infiltration in diabetic cardiomyopathy: new insights from bioinformatics analysis |
title | Role of mitochondrial metabolic disorder and immune infiltration in diabetic cardiomyopathy: new insights from bioinformatics analysis |
title_full | Role of mitochondrial metabolic disorder and immune infiltration in diabetic cardiomyopathy: new insights from bioinformatics analysis |
title_fullStr | Role of mitochondrial metabolic disorder and immune infiltration in diabetic cardiomyopathy: new insights from bioinformatics analysis |
title_full_unstemmed | Role of mitochondrial metabolic disorder and immune infiltration in diabetic cardiomyopathy: new insights from bioinformatics analysis |
title_short | Role of mitochondrial metabolic disorder and immune infiltration in diabetic cardiomyopathy: new insights from bioinformatics analysis |
title_sort | role of mitochondrial metabolic disorder and immune infiltration in diabetic cardiomyopathy: new insights from bioinformatics analysis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9893675/ https://www.ncbi.nlm.nih.gov/pubmed/36726122 http://dx.doi.org/10.1186/s12967-023-03928-8 |
work_keys_str_mv | AT pengcheng roleofmitochondrialmetabolicdisorderandimmuneinfiltrationindiabeticcardiomyopathynewinsightsfrombioinformaticsanalysis AT zhangyanxiu roleofmitochondrialmetabolicdisorderandimmuneinfiltrationindiabeticcardiomyopathynewinsightsfrombioinformaticsanalysis AT langxueyan roleofmitochondrialmetabolicdisorderandimmuneinfiltrationindiabeticcardiomyopathynewinsightsfrombioinformaticsanalysis AT zhangyao roleofmitochondrialmetabolicdisorderandimmuneinfiltrationindiabeticcardiomyopathynewinsightsfrombioinformaticsanalysis |