Comprehensive Analysis of the Immune Infiltrates and Aberrant Pathways Activation in Atherosclerotic Plaque

Abstract

Atherosclerosis is the pathological basis of many cardiovascular and cerebrovascular diseases. The development of gene chip and high-throughput sequencing technologies revealed that the immune microenvironment of coronary artery disease (CAD) in high-risk populations played an important role in the formation and development of atherosclerotic plaques. Three gene expression datasets related to CAD were assessed using high-throughput profiling. CIBERSORT analysis revealed significant differences in five types of immune cells: activated dendritic cells (DCs), T follicular helper cells (Tfhs), resting CD4+ T cells, regulatory T cells (Tregs), and γδ T cells. Immune transcriptome analysis indicated higher levels of inflammatory markers (cytolytic activity, antigen presentation, chemokines, and cytokines) in the cases than in the controls. The level of activated DCs and the lipid clearance signaling score were negatively correlated. We observed a positive correlation between the fraction of Tfhs and lipid biosynthesis. Resting CD4+ T cells and the activity of pathways related to ossification in bone remodeling and glutathione synthesis showed a negative correlation. Gamma delta T cells negatively correlated with IL-23 signaling activity. GSEA revealed a close association with the inflammatory immune microenvironment. The present study revealed that CAD patients may have an inflammatory immune microenvironment and provides a timely update on anti-inflammatory therapies under current investigation.

Phenotypic Changes of Peripheral γδ T Cell and Its Subsets in Patients With Coronary Artery Disease

“…Using high- throughput analysis technology to analyze three gene expression databases related to CAD, a recent study demonstrated that the number of gd T cells infiltrating human atherosclerotic plaques was lower than that in control groups. Meanwhile, the expression levels of immunological function-related genes including the chemokines (CCL5, CX3CL1, CXCL10) in CAD plaques were higher than those in the control group (3). Previous studies have shown that the phenotypic distribution of immune cells differs between carotid atherosclerotic plaques and blood, and the frequencies of CD4 -CD8 -T cells were more abundant in plaques than that in blood.…”

“…The various immune cells, such as monocytes, macrophages, dendritic cells, NK cells of the innate immune system as well as T cells and B cells of the adaptive immune system, are supposed to be involved in all processes of formation and development of atherosclerosis and rupture of vulnerable plaques. Some immune cells that infiltrate into the atherosclerotic plaque and the interactions of cells induce the secretion of proinflammatory cytokines which maintain the atherosclerotic plaque in an inflammatory microenvironment (3). The immunological roles of monocytes, macrophages and CD4 + T cells, which are the most common T cells in plaques and atherosclerotic lesions, have been extensively studied.…”

Diagnostic biomarkers for skin aging

“…Therefore, further studies are needed to explore the molecular mechanism of skin aging. Gene chip technology has led to increased use of gene expression data in clinical research, and microarrays are widely used in the studies related to peripheral blood [27][28][29][30]; however, little is known about the predictive values of different molecular markers of skin aging [31]. Here, we examined the differential expression of genes associated with skin aging and identi ed DEGs through functional analysis.…”

Identification and validation of ferroptosis-related genes and immune infiltration in ischemic cardiomyopathy

“…Kushnareva et al found that the expression of PD-L1 and the number of CD3+ cells in endothelial cells increased in the myocardium of patients with ischemic heart failure (11). Besides, several bioinformatic comprehensive analyses have also confirmed the difference in immune infiltrates between patients with coronary artery disease and healthy controls (12,13). However, the mechanisms underlying immune infiltration in ICM remain poorly understood.…”