Expressional and epigenetic alterations of placental matrix metalloproteinase 9 in preeclampsia

Abstract

Preeclampsia is classically defined by the presence of hypertension and proteinuria after 20 weeks gestation and, thus, affects multiple body systems. The etiology of the disease remains poorly understood but it is known that the expression profile of placental genes is modified, including that of several matrix metalloproteinases (MMPs). The objective of this study was to perform a systematic expression analysis of MMP9 genes in normal and pathological placentas, and to pinpoint epigenetic alterations inside the MMP9 promoter region. Placentas were obtained from 20 patients with preeclampsia and 18 normal pregnancies in the third trimester. The methylation status of the promoter regions of MMP9 was analyzed with methylation-sensitive restriction enzymes, followed by polymerase chain reaction amplification. Our study found significantly higher expression levels of MMP9 in placental sections from preeclampsia tissue and this increased expression was well correlated to promoter demethylation. The percentage of unmethylated -712 sites were higher in preeclampsia patients (90%) compared with controls (44%). In conclusion, this study provides evidence that altered synthesis of MMP9 in preeclampsia placentas may result from epigenetic changes of the methylation status of CpG sites in the promoter region.

Fetal programming of pulmonary vascular dysfunction in mice: role of epigenetic mechanisms

“…Along the same lines, preeclampsia, another condition known to predispose the offspring to systemic and pulmonary vascular dysfunction (16,18), is associated with dysmethylation in the placenta (27,32). Taken together, these findings could suggest that epigenetic mechanisms may contribute to vascular dysfunction in offspring of famine and offspring of mothers with preeclampsia in humans.…”

Urinary neutrophil gelatinase-associated lipocalin (NGAL) excretion increases in normal pregnancy but not in preeclampsia

“…Thus, it would be worth examining the production of NGAL in placentas from preeclamptic pregnancies, as NGAL has been detected in trophoblast cells with up-regulated expression in intraamniotic infection [19]. Metalloproteinase 9 (MMP9) is up-regulated in human placenta from women with preeclampsia [20]. As NGAL binds to MMP9, and enhances the action of MMP9, binding between NGAL and MMP9 may be of patophysiological importance in preeclampsia [1,21].…”

Association of cytomegalovirus infection with hypertension risk: a meta-analysis

“…Finally, genomic-related changes could be involved in the mechanism. In particular, DNA methylation of gene promoter region [38–40] and the corresponding changes in mRNA expression [14] are also involved in regulating blood pressure. The studies included there are not enough, so we need more prospective studies to prove the link.…”