Why the study?
Atherosclerosis causes significant morbidity and mortality worldwide, but the molecular mechanisms underlying its pathogenesis remain largely unknown.
Population
Atherosclerotic plaque and normal aortic tissue samples
Comparison
Atherosclerotic lesion tissues vs normal aortic tissues
Design
Integrated epigenetic and transcriptional analysis with RT-qPCR validation
Answers are grounded in this paper and cite their sources.
Supports immune-targeted pathway exploration in atherosclerosis; hypothesis-generating and requires validation before clinical consideration.
BACKGROUND: The clinical consequences of atherosclerosis are significant source of morbidity and mortality throughout the world, while the molecular mechanisms of the pathogenesis of atherosclerosis are largely unknown. METHODS: In this study, we integrated the DNA methylation and gene expression data in atherosclerotic plaque samples to decipher the underlying association between epigenetic and transcriptional regulation. Immune cell classification was performed on the basis of the expression pattern of detected genes. Finally, we selected ten genes with dysregulated methylation and expression levels for RT-qPCR validation. RESULTS: Global DNA methylation profile showed obvious changes between normal aortic and atherosclerotic lesion tissues. We found that differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were highly associated with atherosclerosis by being enriched in atherosclerotic plaque formation-related pathways, including cell adhesion and extracellular matrix organization. Immune cell fraction analysis revealed that a large number of immune cells, especially macrophages, activated mast cells, NK cells, and Tfh cells, were specifically enriched in the plaque. DEGs associated with immune cell fraction change showed that they were mainly related to the level of macrophages, monocytes, resting NK cells, activated CD4 memory T cells, and gamma delta T cells. These genes were highly enriched in multiple pathways of atherosclerotic plaque formation, including blood vessel remodeling, collagen fiber organization, cell adhesion, collagen catalogic process, extractable matrix assembly, and platelet activation. We also validated the expression alteration of ten genes associated with infiltrating immune cells in atherosclerosis. CONCLUSIONS: In conclusion, these findings provide new evidence for understanding the mechanisms of atherosclerotic plaque formation, and provide a new and valuable research direction based on immune cell infiltration.
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Yin et al. (2022) studied this question.
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