ABCA1, TCF7, NFATC1, PRKCZ, and PDGFA DNA methylation as potential epigenetic-sensitive targets in acute coronary syndrome via network analysis. Issue 5 (4th May 2022)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Epigenetics. Volume 17:Issue 5(2022)
• Page Start: 547
• Page End: 563
• Publication Date: 2022-05-04
• Subjects: Acute coronary syndrome -- epigenetics -- DNA methylation -- T lymphocytes; Epigenesis -- Periodicals; Epigenetica; 572.86505
• DOI: 10.1080/15592294.2021.1939481
• Languages: English
• ISSNs: 1559-2294

Abstract

ABSTRACT: 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.