Journal
EPIGENETICS
Volume 17, Issue 5, Pages 547-563Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15592294.2021.1939481
Keywords
Acute coronary syndrome; epigenetics; DNA methylation; T lymphocytes
Funding
- progetto Progetto di Rilevante Interesse Nazionale - Italian Ministry of Research [2017F8ZB89, GR-2016-02364785]
- Italian Ministry of Research
- Italian Association for Cancer Research [IG-23068]
- Regione Campania [CUP: B41C17000080007]
- University of Campania 'Luigi Vanvitelli,' Naples, Italy
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This study conducted an epigenome-wide analysis of CD4(+) and CD8(+) T cells from ACS patients and healthy subjects using RRBS. Differentially methylated regions were identified, providing insight into the role of aberrant methylation in ACS pathogenesis and potential for epigenetic-sensitive biomarkers.
Acute coronary syndrome (ACS) is the most severe clinical manifestation of coronary heart disease. We performed an epigenome-wide analysis of circulating CD4(+) and CD8(+) T cells isolated from ACS patients and healthy subjects (HS), enrolled in the DIANA clinical trial, by reduced-representation bisulphite sequencing (RRBS). In CD4(+) T cells, we identified 61 differentially methylated regions (DMRs) associated with 57 annotated genes (53% hyper- and 47% hypo-methylated) by comparing ACS patients vs HS. In CD8(+) T cells, we identified 613 DMRs associated with 569 annotated genes (28% hyper- and 72% hypo-methylated) in ACS patients as compared to HS. In CD4(+) vs CD8(+) T cells of ACS patients we identified 175 statistically significant DMRs associated with 157 annotated genes (41% hyper- and 59% hypo-methylated). From pathway analyses, we selected six differentially methylated hub genes (NFATC1, TCF7, PDGFA, PRKCB, PRKCZ, ABCA1) and assessed their expression levels by q-RT-PCR. We found an up-regulation of selected genes in ACS patients vs HS (P < 0.001). ABCA1, TCF7, PDGFA, and PRKCZ gene expression was positively associated with CK-MB serum concentrations (r = 0.75, P = 0.03; r = 0.760, P = 0.029; r = 0.72, P = 0.044; r = 0.74, P = 0.035, respectively). This pilot study is the first single-base resolution map of DNA methylome by RRBS in CD4(+) and CD8(+) T cells and provides specific methylation signatures to clarify the role of aberrant methylation in ACS pathogenesis, thus supporting future research for novel epigenetic-sensitive biomarkers in the prevention and early diagnosis of this pathology.
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