DNA methylation status of cytokine biosynthesis genes during hyperhomocysteinemia in Cystathionine Beta‐synthase Heterozygote Mice

Abstract

Epigenetic regulations play a role in the development and progression of cardiovascular diseases. Discovering novel epigenetically regulated genes could provide useful information in understanding hyperhomocysteinemia (HHcy). We have previously shown that HHcy causes cardiovascular dysfunction due to reduced NO bioactivity. Genetic defects in cystathionine beta‐synthase (CBS) can cause severe HHcy. We have shown that CBS deficiency caused HHcy during pregnancy and lead to impairment of cardiac function, increased O2− production and reduced the ability of NO to regulate myocardial O2 consumption probably through NADPH oxidase stimulation. DNA methylation is an epigenetic event that affects cell function by altering gene expression and could be a potential mechanism for regulating gene expression in these animals. As a preliminary study, we carried out a small scale DNA methylation analysis between wild type and CBS (+/−) mice using the Mouse Cytokine Production DNA Methylation PCR array. This array profiles the promoter methylation status of a panel of 24 genes whose role in cytokine biosynthesis has been well documented. The results showed that 8/24 genes represented (such as IL18, Ltb, Smad3&4 and Igf2bp2) were hypermethylated in these animals but to a higher extend in CBS (+/−) mice. This could highlight the importance of epigenetic mechanisms in the progression of HHcy. Supported by HL‐PO1‐43023.