Analysis of Immune Associated Co-Expression Networks Reveals Immune-Related Long Non-Coding RNAs during MI in the Presence and Absence of HDC

Myocardial infarction (MI) is one of the most common cardiovascular diseases. Although previous studies have shown that histidine decarboxylase (HDC), a histamine-synthesizing enzyme, is involved in the stress response and heart remodeling after MI, the mechanism underlying it remains unclear. In th...

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Main Authors: Zhiwei Zhang, Suling Ding, Xiangdong Yang, Junbo Ge
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/14/7401
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author Zhiwei Zhang
Suling Ding
Xiangdong Yang
Junbo Ge
author_facet Zhiwei Zhang
Suling Ding
Xiangdong Yang
Junbo Ge
author_sort Zhiwei Zhang
collection DOAJ
description Myocardial infarction (MI) is one of the most common cardiovascular diseases. Although previous studies have shown that histidine decarboxylase (HDC), a histamine-synthesizing enzyme, is involved in the stress response and heart remodeling after MI, the mechanism underlying it remains unclear. In this study, using <i>Hdc</i>-deficient mice (<i>Hdc</i><sup>−/−</sup> mice), we established an acute myocardial infarction mouse model to explore the potential roles of <i>Hdc</i>/histamine in cardiac immune responses. Comprehensive analysis was performed on the transcriptomes of infarcted hearts. Differentially expressed gene (DEG) analysis identified 2126 DEGs in <i>Hdc</i>-deficient groups and 1013 in histamine-treated groups. Immune related pathways were enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then we used the ssGSEA algorithm to evaluate 22 kinds of infiltrated immunocytes, which indicated that myeloid cells and T memory/follicular helper cells were tightly regulated by <i>Hdc</i>/histamine post MI. The relationships of lncRNAs and the Gene Ontology (GO) functions of protein-coding RNAs and immunocytes were dissected in networks to unveil immune-associated lncRNAs and their roles in immune modulation after MI. Finally, we screened out and verified four lncRNAs, which were closely implicated in tuning the immune responses after MI, including ENSMUST00000191157, ENSMUST00000180693 (PTPRE-AS1), and ENSMUST-00000182785. Our study highlighted the HDC-regulated myeloid cells as a driving force contributing to the government of transmission from innate immunocytes to adaptive immunocytes in the progression of the injury response after MI. We identified the potential role of the <i>Hdc</i>/histamine-lncRNAs network in regulating cardiac immune responses, which may provide novel promising therapeutic targets for further promoting the treatment of ischemic heart disease.
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spelling doaj.art-579e7f0828244fe89a9278b150aedf2e2023-11-22T03:57:56ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012214740110.3390/ijms22147401Analysis of Immune Associated Co-Expression Networks Reveals Immune-Related Long Non-Coding RNAs during MI in the Presence and Absence of HDCZhiwei Zhang0Suling Ding1Xiangdong Yang2Junbo Ge3Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, ChinaInstitutes of Biomedical Sciences, Fudan University, Shanghai 200032, ChinaInstitutes of Biomedical Sciences, Fudan University, Shanghai 200032, ChinaInstitutes of Biomedical Sciences, Fudan University, Shanghai 200032, ChinaMyocardial infarction (MI) is one of the most common cardiovascular diseases. Although previous studies have shown that histidine decarboxylase (HDC), a histamine-synthesizing enzyme, is involved in the stress response and heart remodeling after MI, the mechanism underlying it remains unclear. In this study, using <i>Hdc</i>-deficient mice (<i>Hdc</i><sup>−/−</sup> mice), we established an acute myocardial infarction mouse model to explore the potential roles of <i>Hdc</i>/histamine in cardiac immune responses. Comprehensive analysis was performed on the transcriptomes of infarcted hearts. Differentially expressed gene (DEG) analysis identified 2126 DEGs in <i>Hdc</i>-deficient groups and 1013 in histamine-treated groups. Immune related pathways were enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then we used the ssGSEA algorithm to evaluate 22 kinds of infiltrated immunocytes, which indicated that myeloid cells and T memory/follicular helper cells were tightly regulated by <i>Hdc</i>/histamine post MI. The relationships of lncRNAs and the Gene Ontology (GO) functions of protein-coding RNAs and immunocytes were dissected in networks to unveil immune-associated lncRNAs and their roles in immune modulation after MI. Finally, we screened out and verified four lncRNAs, which were closely implicated in tuning the immune responses after MI, including ENSMUST00000191157, ENSMUST00000180693 (PTPRE-AS1), and ENSMUST-00000182785. Our study highlighted the HDC-regulated myeloid cells as a driving force contributing to the government of transmission from innate immunocytes to adaptive immunocytes in the progression of the injury response after MI. We identified the potential role of the <i>Hdc</i>/histamine-lncRNAs network in regulating cardiac immune responses, which may provide novel promising therapeutic targets for further promoting the treatment of ischemic heart disease.https://www.mdpi.com/1422-0067/22/14/7401myocardial infarctionhistidine decarboxylaseimmune infiltrationlncRNA
spellingShingle Zhiwei Zhang
Suling Ding
Xiangdong Yang
Junbo Ge
Analysis of Immune Associated Co-Expression Networks Reveals Immune-Related Long Non-Coding RNAs during MI in the Presence and Absence of HDC
International Journal of Molecular Sciences
myocardial infarction
histidine decarboxylase
immune infiltration
lncRNA
title Analysis of Immune Associated Co-Expression Networks Reveals Immune-Related Long Non-Coding RNAs during MI in the Presence and Absence of HDC
title_full Analysis of Immune Associated Co-Expression Networks Reveals Immune-Related Long Non-Coding RNAs during MI in the Presence and Absence of HDC
title_fullStr Analysis of Immune Associated Co-Expression Networks Reveals Immune-Related Long Non-Coding RNAs during MI in the Presence and Absence of HDC
title_full_unstemmed Analysis of Immune Associated Co-Expression Networks Reveals Immune-Related Long Non-Coding RNAs during MI in the Presence and Absence of HDC
title_short Analysis of Immune Associated Co-Expression Networks Reveals Immune-Related Long Non-Coding RNAs during MI in the Presence and Absence of HDC
title_sort analysis of immune associated co expression networks reveals immune related long non coding rnas during mi in the presence and absence of hdc
topic myocardial infarction
histidine decarboxylase
immune infiltration
lncRNA
url https://www.mdpi.com/1422-0067/22/14/7401
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AT xiangdongyang analysisofimmuneassociatedcoexpressionnetworksrevealsimmunerelatedlongnoncodingrnasduringmiinthepresenceandabsenceofhdc
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