Prenatal Exposure to apoE Deficiency and Postnatal Hypercholesterolemia Are Associated with Altered Cell-Specific Lysine Methyltransferase and Histone Methylation Patterns in the Vasculature

We recently demonstrated that neointima formation of adult heterozygous apolipoprotein E (apoE(+/-)) offspring from hypercholesterolemic apoE(-/-) mothers was significantly increased as compared with genetically identical apoE(+/-) offspring from normocholesterolemic wild-type mothers. Since atherosclerosis is the consequence of a complex microenvironment and local cellular interactions, the effects of in utero programming and type of postnatal diet on epigenetic histone modifications in the vasculature were studied in both groups of offspring. An immunohistochemical approach was used to detect cell-specific histone methylation modifications and expression of accompanying lysine methyltransferases in the carotid arteries. Differences in histone triple-methylation modifications in vascular endothelial and smooth muscle cells revealed that the offspring from apoE(-/-) mothers had significantly different responses to a high cholesterol diet when compared with offspring from wild-type mothers. Our results suggest that both in utero programming and postnatal hypercholesterolemia affect epigenetic patterning in the vasculature, thereby providing novel insights regarding initiation and progression of vascular disease in adults. (Am J Pathol 2010, 176:542-548; DOI: 10.2353/ajpath.2010.090031)