Veena Dhawan
Postgraduate Institute of Medical Education and Research, India
Title: Aberrant DNA methylation of M1-macrophage genes in coronary artery disease
Biography
Biography: Veena Dhawan
Abstract
Macrophage heterogeneity within atherosclerotic lesions has attracted much interest owing to the importance of balance between M1 and M2 population. Though, it remains unknown how macrophage heterogeneity is regulated. Moreover, the regulation of macrophage polarization and activation also involve DNA methylation. However, it remains unknown which genes are directly regulated by DNA methylation. The aim of the study was to assess the gene-specific promoter DNA methylation status of M1/ M2 macrophage polarization markers STAT1, STAT6, MHC2, IL12b, iNOS, JAK1, JAK2 and SOCS5 in peripheral blood mononuclear cells of CAD patients. A casecontrol study was performed with 25 CAD patients and 25 controls to investigate the gene-specific promoter DNA methylation status using MS-HRM analysis. Our data indicates that there was a clear-cut difference in the pattern of gene-specific promoter DNA methylation of above mentioned genes in CAD patients as compared to controls. A consistent hypomethylated pattern was observed for most of the samples including both CAD patients and controls, which was heterogeneous DNA methylation as evident by their melting profiles. A significant difference was observed between the mean percentage methylation of STAT1, IL12b, MHC2, iNOS, JAK1 and JAK2 in CAD patients and control subjects. Our data showed that MS-HRM assay is a rapid and inexpensive method for qualitatively investigation and identification of aberrant gene-specific promoter DNA methylation changes in CAD. Since, monocytes and macrophages play a significant role in atherosclerosis, we propose that epigenetic markers including gene-specific promoter DNA methylation based on monocyte/macrophage might aid as diagnostic markers or drug targets for clinical application. Therefore, skewing the M1/M2 balance towards a more preferable phenotype through DNA methylation-related interventions may offer novel possibilities for atherosclerotic disease management.