Atherogenic Factors and Their Epigenetic Relationships

Abstract

Hypercholesterolemia, homocysteine, oxidative stress, and hyperglycemia have been recognized as the major risk factors for atherogenesis. Their impact on the physiology and biochemistry of vascular cells has been widely demonstrated for the last century. However, the recent discovery of the role of epigenetics in human disease has opened up a new field in the study of atherogenic factors. Thus, epigenetic tags in endothelial, smooth muscle, and immune cells seem to be differentially affected by similar atherogenic stimuli. This paper summarizes some recent works on expression of histone-modifying enzymes and DNA methylation directly linked to the presence of risk factors that could lead to the development or prevention of the atherosclerotic process.

Epigenetic Modulation of Intestinal Cholesterol Transporter Niemann-Pick C1-like 1 (NPC1L1) Gene Expression by DNA Methylation

“…DNMT3L lacks the cytosine methylation activity and functions as a regulatory factor in germ cells (17). The functional roles of DNMT2 are slowly emerging, and recent studies suggested its involvement in tRNA methylation (17). Our findings show that the attenuation of either DNMT1 or DNMT3B alone did not affect NPC1L1 mRNA expression.…”

“…DNA methylation is mediated by DNMTs that catalyze the transfer of methyl groups from S-adenosylmethionine to the cytosine residue in the CpG dinucleotides (17). Three distinct families of DNMTs, DNMT1, DNMT2, and DNMT3, have been identified in mammals.…”

“…DNMT3 family consists of three members as follows: DNMT3A, DNMT3B, and DNMT3L. DNMT3L lacks the cytosine methylation activity and functions as a regulatory factor in germ cells (17). The functional roles of DNMT2 are slowly emerging, and recent studies suggested its involvement in tRNA methylation (17).…”

“…Four DNMT isoforms have previously been identified as follows: DNMT1, DNMT2, DNMT3A, and DNMT3B (17) . Fig.…”

Abnormal lipid metabolism in metabolic syndrome: an epigenetic perspective

“…In an in-vivo model using 20-week old female apo E +/-mouse offspring from apo E -/-and wild-type mothers, it was shown that both prenatal induced and diet-induced hypercholesterolemia influenced histone methylation and lysine methyltransferase expression in vasculature. Moreover, these epigenetic modifications were different in endothelial cells and smooth muscle cells, suggesting the existence of a cell -specific responsiveness to a similar stimulating factor (11,12).…”