VCAM1 expression in the myocardium is associated with the risk of heart failure and immune cell infiltration in myocardium
Abstract Ischemic heart disease (IHD) and dilated cardiomyopathy (DCM) are the two most common etiologies of heart failure (HF). Both forms share common characteristics including ventricle dilation in the final stage. Immune mechanisms in HF are increasingly highlighted and have been implicated in t...
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| Autores principales: | , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/72f853f49f714da49f1d3784292cbaf1 |
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| Sumario: | Abstract Ischemic heart disease (IHD) and dilated cardiomyopathy (DCM) are the two most common etiologies of heart failure (HF). Both forms share common characteristics including ventricle dilation in the final stage. Immune mechanisms in HF are increasingly highlighted and have been implicated in the pathogeneses of IHD and DCM. A better understanding of adhesion molecule expression and correlated immune cell infiltration could enhance disease detection and improve therapeutic targets. This study was performed to explore the common mechanisms underlying IHD and DCM. After searching the Gene Expression Omnibus database, we selected the GSE42955, GSE76701, GSE5406, GSE133054 and GSE57338 datasets for different expressed gene (DEGs) selection and new cohort establishment. We use xcell to calculate immune infiltration degree, ssGSEA and GSEA to calculate the pathway and biological enrichment score, consensus cluster to identify the m6A modification pattern, and LASSO regression to make risk predicting model and use new combined cohort to validate the results. The screening stage revealed that vascular cell adhesion molecule 1 (VCAM1) play pivotal roles in regulating DEGs. Subsequent analyses revealed that VCAM1 was differentially expressed in the myocardium and involved in regulating immune cell infiltration. We also found that dysregulated VCAM1 expression was associated with a higher risk of HF by constructing a clinical risk-predicting model. Besides, we also find a connection among the m6A RNA modification ,expression of VCAM1 and immune regulation. Those connection can be linked by the Wnt pathway enrichment alternation. Collectively, our results suggest that VCAM-1 have the potential to be used as a biomarker or therapy target for HF and the m6A modification pattern is associated with the VCAM1 expression and immune regulation. |
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