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.