Study of sRAGE, HMGB1, AGE, and S100A8/A9 Concentrations in Plasma and in Serum-Extracted Extracellular Vesicles of Pregnant Women With Preterm Premature Rupture of Membranes

Abstract

There was a correlation between plasma and serum-extracted extracellular vesicle concentrations of sRAGE, AGE, HMGB1, and S100A8/A9. Our results suggest that the rupture of fetal membranes (physiological or premature) is accompanied by a variation in plasma concentrations of sRAGE, HMGB1, and AGE. The study of RAGE and its main ligands in extracellular vesicles did not give additional insight into the pathophysiological process conducting to PPROM.

High‐mobility group box 1 is a driver of inflammation throughout pregnancy

“…These data further support the idea that HMGB1 may be an important contributor to the initiation of fetal membrane weakening in rupture of membranes (ROM) and pPROM. Additionally, HMGB1 plasma and serum‐extracted extracellular vesicles levels throughout pregnancy have been assessed and HMGB1 plasma concentrations and serum‐extracted extracellular vesicles were found to significantly correlate with both pPROM and normal fetal membranes to promote inflammation 43 . Together, these data suggest that plasma concentrations may contribute to fetal membrane rupture in both normal conditions and pPROM as inflammation is central to membrane weakening in both circumstances.…”

“…Therefore, although the assessment of the precise mechanisms of pregnancy complications is often not studied until the fetus is born, there are few situations in which samples can be collected from less invasive approaches such as the assessment of maternal plasma or serum 71 . However, two recent publications were able to elegantly measure the levels of HMGB1 over all of three trimesters and at delivery, the first assessing levels from cultured fetal membranes 42 and the other levels in the maternal circulation throughout pregnancy 43 …”

“…The increased concentration or expression of HMGB1 has been detected in term tissues 35‐38 ; however, there is evidence to suggest HMGB1 also has an adverse role that promotes and contributes to pregnancy complications that include preterm premature rupture of the membranes (pPROM) and infection‐initiated inflammation (Table 1). 39‐49 …”

“…3 The increased concentration or expression of HMGB1 has been detected in term tissues [35][36][37][38] ; however, there is evidence to suggest HMGB1 also has an adverse role that promotes and contributes to pregnancy complications that include preterm premature rupture of the membranes (pPROM) and infection-initiated inflammation (Table 1). [39][40][41][42][43][44][45][46][47][48][49] Therefore, the aims of this review are threefold: (a) to describe how important HMGB1 is to drive inflammation in the different stages of pregnancy, (b) to describe the current knowledge of HMGB1 in pregnancy pathologies driven by inflammation, and (c) to highlight the potential of HMGB1 as a biomarker and therapeutic target in pregnancy.…”

Pathophysiological Implication of Pattern Recognition Receptors in Fetal Membranes Rupture: RAGE and NLRP Inflammasome

“…Later, other studies reported an increase in plasmatic esRAGE levels in pPROM but also in placental RAGE levels [ 63 , 98 ]. However, more recently, in 2020, another study found no significant difference in plasmatic sRAGE levels between pPROM and term rupture [ 99 ].…”