Details

Autor(en) / Beteiligte

• Infante, Teresa
• Franzese, Monica
• Ruocco, Antonio
• Schiano, Concetta
• Affinito, Ornella
• Pane, Katia
• Memoli, Domenico
• Rizzo, Francesca
• Weisz, Alessandro
• Bontempo, Paola
• Grimaldi, Vincenzo
• Berrino, Liberato
• Soricelli, Andrea
• Mauro, Ciro
• Napoli, Claudio

Titel

ABCA1, TCF7, NFATC1, PRKCZ, and PDGFA DNA methylation as potential epigenetic-sensitive targets in acute coronary syndrome via network analysis

Ist Teil von

• Epigenetics, 2022-05, Vol.17 (5), p.547-563

Ort / Verlag

United States: Taylor & Francis

Erscheinungsjahr

2022

Quelle

Taylor & Francis Journals Auto-Holdings Collection

Beschreibungen/Notizen

• 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.