Dataset Information

Differential Expression of Subsets of Genes Related to HDL Metabolism and Atherogenesis in the Peripheral Blood in Coronary Artery Disease.

ABSTRACT: Differential expression of genes (DEGs) in coronary artery disease (CAD) and the association between transcript level and high-density lipoprotein cholesterol (HDL-C) were studied with 76 male patients with CAD and 63 control patients. The transcript level of genes related to HDL metabolism (24 genes) and atherosclerosis-prone (41 genes) in RNA isolated from peripheral blood mononuclear cells was measured by real-time RT-PCR. Twenty-eight DEGs were identified. The expression of cholesterol transporters, ALB, APOA1, and LCAT was down-regulated, while the expression of AMN, APOE, LDLR, LPL, PLTP, PRKACA, and CETP was up-regulated. The systemic inflammation in CAD is evidenced by the up-regulation of IL1B, TLR8, CXCL5, and TNFRSF1A. For the controls, TLR8 and SOAT1 were negative predictors of the HDL-C level. For CAD patients, PRKACG, PRKCQ, and SREBF1 were positive predictors, while PRKACB, LCAT, and S100A8 were negative predictors. For CAD patients, the efficiency of reverse cholesterol transport is 73-79%, and intracellular free cholesterol seems to accumulate at hyperalphalipoproteinemia. Both atheroprotective (via S100A8) and proatherogenic (via SREBF1, LCAT, PRKACG, PRKACB, and PRKCQ) associations of gene expression with HDL-C determine HDL functionality in CAD patients. The selected key genes and involved pathways may represent HDL-specific targets for the diagnosis and treatment of CAD and atherosclerosis.

SUBMITTER: Dergunov AD

PROVIDER: S-EPMC10452992 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Differential Expression of Subsets of Genes Related to HDL Metabolism and Atherogenesis in the Peripheral Blood in Coronary Artery Disease.

Dergunov Alexander D AD Nosova Elena V EV Rozhkova Alexandra V AV Vinogradina Margarita A MA Baserova Veronika B VB Popov Mikhail A MA Limborska Svetlana A SA Dergunova Liudmila V LV

Current issues in molecular biology 20230816 8

Differential expression of genes (DEGs) in coronary artery disease (CAD) and the association between transcript level and high-density lipoprotein cholesterol (HDL-C) were studied with 76 male patients with CAD and 63 control patients. The transcript level of genes related to HDL metabolism (24 genes) and atherosclerosis-prone (41 genes) in RNA isolated from peripheral blood mononuclear cells was measured by real-time RT-PCR. Twenty-eight DEGs were identified. The expression of cholesterol trans ...[more]

PMID: 37623250

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Project description:BackgroundThe peripheral blood gene expression profile of patients with coronary artery disease (CAD) has not been fully resolved. The aim of this study was to further analyze the peripheral blood transcriptome information of CAD patients and to uncover key genes and regulatory mechanisms in the pathogenesis and disease progression of CAD.MethodsThe Gene Expression Omnibus (GEO) database was applied to screen out differentially expressed genes (DEGs) in the peripheral blood of CAD patients, and the DEGs were subjected to Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). The core genes were screened by GO, KEGG, and GSEA, and the gene-gene interaction (GGI) and protein-protein interaction (PPI) networks of DEGs were constructed. The GeneCards database was used to obtain CAD-related genes, and the GEO dataset was used to obtain intersecting genes. The intersecting genes were analyzed for bioenrichment and prediction of potential therapeutic agents, and predictive models were constructed for the intersecting genes. Finally, immune infiltrating cells from the GEO dataset were analyzed.ResultsA total of 79 DEGs were screened in the peripheral blood of CAD patients, of which three were autophagy-related genes. Biological enrichment analysis showed that the DEGs were associated with metabolic pathways, and vascular smooth muscle contraction and were mainly involved the MAPK signaling pathway, metabolic pathways, and the PI3K-Akt signaling pathway. The S100A8, ENTPD1, and MMP9 further screened were screened. A total of 11 CAD crossover genes and 75 potential therapeutic agents were obtained, and the column line graph prediction models constructed for S100A8, HSPB1, F5, MMP9, and PDE9A had good predictive power. There were significant differences in immune cells in CAD patients compared to healthy individuals, especially in T cells regulatory (Tregs) and B cells naïve.ConclusionsThe peripheral blood of CAD patients screened by the GEO dataset was significantly different from that of the healthy population, and the DEGs and intersecting genes were involved in numerous key biological processes that may be involved in the development and progression of CAD and could serve as its regulatory sites and therapeutic drug targets.

Project description:Coronary atherosclerotic heart disease (CAD) is a chronic inflammatory cardiovascular disease with high morbidity and mortality. Growing data indicate that many immune cells are involved in the development of atherosclerosis. However, the immunological roles of γδ T cells in the initiation and progression of CAD are not fully understood. Here, we used flow cytometry to determine phenotypical changes of γδ T cells and their subpopulations in peripheral blood samples collected from 37 CAD patients. The Pearson correlation coefficient was used to analyze the relationship between the clinical parameter (serum LDL-C level) and the changes of immunophenotypes of γδ T cells. Our results demonstrated that the frequencies and absolute numbers of total γδ T cells and Vδ2+ T cells were significantly decreased in CAD patients when compared to healthy individuals. However, the proportion of Vδ1+ T cells was much lower in CAD patients than that of healthy individuals. Most importantly, a significant alteration of the Vδ1/Vδ2 ratio was found in CAD patients. In addition, a series of surface markers that are associated with costimulatory signals (CD28, CD40L, CD80, CD86), activation levels (CD69, CD25, HLA-DR), activating NK cell receptors (NKp30, NKp46, NKG2D) and inhibitory receptors (PD-1, CTLA-4, PD-1, Tim-3) were determined and then analyzed in the total γδ T cells, Vδ2+T cells and Vδ2-T cells of CAD patients and healthy individuals. The data demonstrated that immunological activities of total γδ T cells, Vδ2+T cells, and Vδ2-T cells of CAD patients were much lower than those in healthy individuals. Moreover, we found that there were positive correlations between the serum LDL-C levels and frequencies of CD3+γδ+ T cells, CD69+Vδ2+T cells, NKG2D+Vδ2+T cells, and NKp46+Vδ2+T cells. By contrast, there was an inverse correlation between the levels of serum LDL-C and the frequencies of CD69+Vδ2-T cells and NKp46+Vδ2-T cells. Accordingly, these findings could help us to better understand the roles of γδ T cells in the CAD, and shed light on the development of novel diagnostic techniques and therapeutic strategies by targeting γδ T cells for CAD patients.

Project description:Monocytes are associated with human cardiovascular disease progression. Monocytes are segregated into three major subsets: classical (cMo), intermediate (iMo), and nonclassical (nMo). Recent studies have identified heterogeneity within each of these main monocyte classes, yet the extent to which these subsets contribute to heart disease progression is not known. Peripheral blood mononuclear cells (PBMC) were obtained from 61 human subjects within the Coronary Assessment of Virginia (CAVA) Cohort. Coronary atherosclerosis severity was quantified using the Gensini Score (GS). We employed high-dimensional single-cell transcriptome and protein methods to define how human monocytes differ in subjects with low to severe coronary artery disease. We analyzed 487 immune-related genes and 49 surface proteins at the single-cell level using Antibody-Seq (Ab-Seq). We identified six subsets of myeloid cells (cMo, iMo, nMo, plasmacytoid DC, classical DC, and DC3) at the single-cell level based on surface proteins, and we associated these subsets with coronary artery disease (CAD) incidence based on Gensini score (GS) in each subject. Only frequencies of iMo were associated with high CAD (GS > 32), adj.p = 0.024. Spearman correlation analysis with GS from each subject revealed a positive correlation with iMo frequencies (r = 0.314, p = 0.014) and further showed a robust sex-dependent positive correlation in female subjects (r = 0.663, p = 0.004). cMo frequencies did not correlate with CAD severity. Key gene pathways differed in iMo among low and high CAD subjects and between males and females. Further single-cell analysis of iMo revealed three iMo subsets in human PBMC, distinguished by the expression of HLA-DR, CXCR3, and CD206. We found that the frequency of immunoregulatory iMo_HLA-DR+CXCR3+CD206+ was associated with CAD severity (adj.p = 0.006). The immunoregulatory iMo subset positively correlated with GS in both females (r = 0.660, p = 0.004) and males (r = 0.315, p = 0.037). Cell interaction analyses identified strong interactions of iMo with CD4+ effector/memory T cells and Tregs from the same subjects. This study shows the importance of iMo in CAD progression and suggests that iMo may have important functional roles in modulating CAD risk, particularly among females.

Dataset Information

Differential Expression of Subsets of Genes Related to HDL Metabolism and Atherogenesis in the Peripheral Blood in Coronary Artery Disease.

Publications

Differential Expression of Subsets of Genes Related to HDL Metabolism and Atherogenesis in the Peripheral Blood in Coronary Artery Disease.

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