Title:LIMD2 is the Signature of Cell Aging-immune/Inflammation in Acute
Myocardial Infarction
Volume: 31
Issue: 17
Author(s): Ping Tao, Xiaoming Chen, Lei Xu, Junteng Chen, Qinqi Nie, Mujuan Xu*Jianyi Feng*
Affiliation:
- The Fourth Clinical
Medical College, Guangzhou University of Chinese Medicine, Shenzhen, 518000, China
- Department
of Intensive Care Unit, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518000, China
- Department of
Cardiology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China
Keywords:
Acute myocardial infarction, cell aging, immune, inflammation, ceRNAs, LIMD2.
Abstract:
Background: Acute myocardial infarction (AMI) is an age-dependent cardiovascular
disease in which cell aging, immunity, and inflammatory factors alter the course; however, cell
aging-immune/inflammation signatures in AMI have not been investigated.
Methods: Based on the GEO database to obtain microRNA (miRNA) sequencing, mRNA sequencing
and single-cell sequencing data, and utilizing the Seurat package to identify AMI-associated
cellular subpopulations. Subsequently, differentially expressed miRNAs and mRNAs
were screened to establish a network of competing endogenous RNAs (ceRNAs). Senescence
and immunity scores were calculated by single sample gene set enrichment analysis (ssGSEA),
ESTIMATE and CIBERSORT algorithms, and the Hmisc package was used to screen for genes
with the highest correlation with senescence and immunity scores. Finally, protein-protein interaction
(PPI) and molecular docking analyses were performed to predict potential therapeutic
agents for the treatment of AMI.
Results: Four cell types (Macrophage, Fibroblast, Endothelial cells, CD8 T cells) were identified
in AMI, and CD8 T cells exhibited the lowest cell aging activity. A ceRNA network of miRNAs-
mNRA interactions was established based on the overlapping genes in differentially expressed
miRNAs (DEmiRNAs) target genes and differentially expressed mRNAs (DEmRNAs).
Twenty-four marker genes of CD8 T cells were observed. LIMD2 was identified as cell aging-
immune/inflammation-related hub gene in AMI. This study also identified a potential therapeutic
network of DB03276-LIMD2-AMI, which showed excellent and stable binding status between
DB03276-LIMD2.
Conclusion: This study identified LIMD2 as a cell aging-immune/inflammation-related hub
gene. The understanding of the pathogenesis and therapeutic mechanisms of AMI was enriched
by the ceRNA network and DB03276-LIMD2-LAMI therapeutic network.