Low Molecular Weight Heparin (LMWH) modulation of placental HMGB1/RAGE axis: novel understanding of Preeclampsia management. Zenerino,

Preeclampsia (PE) is a severe pregnancy-related syndrome characterized by exacerbated placental inflammation. LMWH has been used during PE since several trials described its anti-inflammatory effect. Nevertheless, LMWH mechanisms of action on the placental tissue are still unclear. HMGB1 is a transcription factor with an extracellular cytokine-like function that plays a pivotal role in the inflammatory process. HMGB1 bound to its receptor RAGE (Receptor for Advanced Glycation End products) is able to induce the transcription of the pro-inflammatory cytokine TNF-α and IL-6. LMWH binds to HMGB1 in-vitro, thus changing its structural conformation and inhibiting its activity. Since HMGB1 has been previously found up-regulated in PE, in the present study we investigated LMWH’s modulation of HMGB1/RAGE axis and its targets TNF-α and IL-6 in the placental tissues