3.1.3. Maternal Endothelial Cells

There is limited access to maternal vessels in pregnancy, nevertheless DNA methylation was assessed from this material in 2012 using the 27K methylation array of Illumina [213]. From 14.495 genes interrogated by the array, 65 genes were identified as hypomethylated in PE. Clustering leads to identify biological processes such as smooth muscle contraction, thrombosis, inflammation, redox homeostasis, sugar metabolism and amino acid metabolism. These alterations of the maternal endothelium sugges<sup>t</sup> potential e ffects on cardiovascular life of the mother after preeclampsia. Focusing on collagen metabolism, the authors revealed an increased expression of MMP1 and MMP8 in vascular smooth muscle cells and infiltrating neutrophils of omental arteries of preeclamptic women, which was associated with reduced methylation in the promoters of both genes in pathological patients compared to control patients [213]. In the same study, several other MMPs, showed reduced hypomethylation in PE patients albeit with lower significance [214,215]. Moreover, pregnan<sup>t</sup> women under dietary supplementation may restore the reduced methylation in the promoters of these genes and be protected against the development of PE. Interestingly, all these MMPs genes are located in chromosome 11, which may be indicative of a specific sensitivity of this chromosome to epigenetic changes caused by oxidative stress during the development of the pathology. The same team reported

the reduced methylation in the promoter region of TBXAS1 gene in correlation with increased gene and protein expression of thromboxane synthase in vascular smooth muscle, endothelium and infiltrating neutrophils [215]. Increased levels of thromboxane synthase induce the overproduction of thromboxane A2, a potent vasoconstrictor and platelet activator, contributing to hypertension and coagulation abnormalities classically related to PE.
