Genetic and Epigenetic Changes of Intercellular Communication Genes During Multistage Carcinogenesis

The myocardium is a highly structured tissue consisting of different cell types including cardiomyocytes, endothelial cells, fibroblasts, smooth muscle cells, inflammatory cells, and stem cells. Microvascular endothelial cells are the most abundant cell type in the myocardium and play crucial roles during cardiac development, in normal adult myocardium, and during myocardial diseases such as heart failure. In the last decade, epigenetic changes have been described regulating cellular function in almost every cell type in the organism. Here, we review recent evidence on different epigenetic changes that regulate intercellular communication in normal myocardium and during myocardial diseases, including cardiac remodeling. Epigenetic changes influence many intercellular communication signaling systems, including the nitric oxide, angiotensin, and endothelin signaling systems. In this review, we go beyond discussing classic endothelial function (for instance nitric oxide secretion) and will discuss epigenetic regulation of intercellular communication.

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Cardiovascular Risk After SARS-CoV-2 Infection Is Mediated by IL18/IL18R1/HIF-1 Signaling Pathway Axis

Frontiers in Immunology ◽

10.3389/fimmu.2021.780804 ◽

2022 ◽

Vol 12 ◽

Author(s):

Liwei Zhang ◽

Mingxing Li ◽

Zhiwei Wang ◽

Peng Sun ◽

Shunbo Wei ◽

...

Keyword(s):

Cardiovascular Risk ◽

Signaling Pathway ◽

Intercellular Communication ◽

Proteomic Analysis ◽

Type I ◽

Epigenetic Changes ◽

Communication Analysis ◽

Mek Inhibitors ◽

Cardiovascular Protection ◽

Key Pathways

ObjectivesCurrently, cardiovascular risk associated with COVID-19 has been brought to people’s attention, but the mechanism is not clear. The aim of this study is to elucidate the mechanisms based on multiple omics data.MethodologyWeighted gene co-expression network analysis (WGCNA) was used to identify key pathways. Combination analysis with aneurysm and atherosclerosis related pathways, hypoxia induced factor-1 (HIF-1) signaling were identified as key pathways of the increased cardiovascular risk associated with COVID-19. ScMLnet algorithm based on scRNA-seq was used to explore the regulation of HIF-1 pathway by intercellular communication. Proteomic analysis was used to detect the regulatory mechanisms between IL18 and HIF-1 signaling pathway. Pseudo time locus analysis was used to study the regulation of HIF1 signaling pathway in macrophages and vascular smooth muscle cells (VSMC) phenotypic transformation. The Virtual Inference of protein-activity by Enriched Regulon (VIPER) analysis was used to study the activity of regulatory proteins. Epigenetic analysis based on methylation revealed epigenetic changes in PBMC after SARS-CoV-2 infection. Potential therapeutic compounds were explored by using Cmap algorithm.ResultsHIF-1 signaling pathway is a common key pathway for aneurysms, atherosclerosis and SARS-CoV-2 infection. Intercellular communication analysis showed that macrophage-derived interleukin-18 (IL-18) activates the HIF-1 signaling pathway through IL18R1. Proteomic analysis showed that IL18/IL18R1 promote NF-κB entry into the nucleus, and activated the HIF-1 signaling pathway. Macrophage-derived IL18 promoted the M1 polarization of macrophages and the syntactic phenotype transformation of VSMCs. MAP2K1 mediates the functional regulation of HIF-1 signaling pathway in various cell types. Epigenetic changes in PBMC after COVID-19 infection are characterized by activation of the type I interferon pathway. MEK inhibitors are the promising compounds for the treatment of HIF-1 overactivation.ConclusionsThe IL18/IL18R1/HIF1A axis is expected to be an therapeutic target for cardiovascular protection after SARS-CoV-2 infection. MEK inhibitors may be an choice for cardiovascular protection after SARS-COV-2 infection

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A new role for AT1 and AT2-receptors in modulating cyclic stretch effects on organization of intercellular communication via gap junctions in cardiac cells

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0031-1297665 ◽

2012 ◽

Vol 60 (S 01) ◽

Author(s):

S Dhein ◽

D Apel ◽

A Salameh ◽

A Woiton ◽

FW Mohr

Keyword(s):

Gap Junctions ◽

Intercellular Communication ◽

Cardiac Cells ◽

Cyclic Stretch ◽

At2 Receptors

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Intercellular Communication Induction

10.32388/dtaold ◽

2020 ◽

Author(s):

Keyword(s):

Intercellular Communication

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THE ROLE OF THE GENETIC ABNORMALITIES, EPIGENETIC AND microRNA IN THE PROGNOSIS OF CHRONIC LYMPHOCYTIC LEUKEMIA

Experimental Oncology ◽

10.31768/2312-8852.2018.40(4):261-267 ◽

2018 ◽

Vol 40 (4) ◽

pp. 261-267 ◽

Cited By ~ 5

Author(s):

K Tari ◽

Z Shamsi ◽

H Reza Ghafari ◽

A Atashi ◽

M Shahjahani ◽

...

Keyword(s):

B Cells ◽

Chronic Lymphocytic Leukemia ◽

Kinase Inhibitors ◽

Bone Marrow Involvement ◽

P53 Mutation ◽

Lymphocytic Leukemia ◽

Gene Promoters ◽

Epigenetic Changes ◽

Genetic Changes ◽

Trisomy 12

Chronic lymphocytic leukemia (CLL) is increased proliferation of B-cells with peripheral blood and bone marrow involvement, which is usually observed in older people. Genetic mutations, epigenetic changes and miRs play a role in CLL pathogenesis. Del 11q, del l17q, del 6q, trisomy 12, p53 and IgVH mutations are the most important genetic changes in CLL. Deletion of miR-15a and miR-16a can increase bcl2 gene expression, miR-29 and miR-181 deletions decrease the expression of TCL1, and miR-146a deletion prevents tumor metastasis. Epigenetic changes such as hypo- and hypermethylation, ubiquitination, hypo- and hyperacetylation of gene promoters involved in CLL pathogenesis can also play a role in CLL. Expression of CD38 and ZAP70, presence or absence of mutation in IgVH and P53 mutation are among the factors involved in CLL prognosis. Use of monoclonal antibodies against surface markers of B-cells like anti-CD20 as well as tyrosine kinase inhibitors are the most important therapeutic approaches for CLL.

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