Objectives: Preeclampsia (PE) is a severe pregnancy-related syndrome characterized by exacerbated placental inflammation. LMWH is widely 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 able to induce pro-inflammatory TNFα and IL-6 molecules. 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 and its targets TNFα and IL-6 in the placental tissue. Methods: Twenty-eight normal placental villous explants were treated for 48h with different concentrations of LMWH (Parnaparin 50U, 5U, 0.5U). HMGB1, TNFα and IL-6 mRNA expression was assessed by Real Time PCR while HMGB1 protein expression was analyzed by Western Blot analysis. Results: While 50U and 5U were toxic for our in-vitro model, we reported significantly decreased gene expression levels of HMGB1, TNFα and IL-6 in placental villous explants treated with LMWH 0.5U vs untreated controls. In contrast, HMGB1 protein levels were increased in LMWH 0.5U explants compared to controls. Conclusion: Herein, we described a direct effect of LMWH on placental HMGB1 modulation. Indeed, HMGB1 protein increase accompanied by decreased TNFα and IL-6 expression in LMWH villous explants confirm the anti-inflammatory effect of heparin and suggest that it is mediated by structural modifications of HMGB1 able to promote its accumulation and to inhibit its function. Further investigations are required.

Anti-inflammatory effect of Low Molecular Weight Heparin (LMWH) is mediated by Placental High Mobility Group Box 1 (HMGB1) Modulation: New Therapeutic Perspectives for Preeclampsia

NUZZO, ANNA MARIA;TODROS, Tullia;ROLFO, Alessandro
2013

Abstract

Objectives: Preeclampsia (PE) is a severe pregnancy-related syndrome characterized by exacerbated placental inflammation. LMWH is widely 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 able to induce pro-inflammatory TNFα and IL-6 molecules. 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 and its targets TNFα and IL-6 in the placental tissue. Methods: Twenty-eight normal placental villous explants were treated for 48h with different concentrations of LMWH (Parnaparin 50U, 5U, 0.5U). HMGB1, TNFα and IL-6 mRNA expression was assessed by Real Time PCR while HMGB1 protein expression was analyzed by Western Blot analysis. Results: While 50U and 5U were toxic for our in-vitro model, we reported significantly decreased gene expression levels of HMGB1, TNFα and IL-6 in placental villous explants treated with LMWH 0.5U vs untreated controls. In contrast, HMGB1 protein levels were increased in LMWH 0.5U explants compared to controls. Conclusion: Herein, we described a direct effect of LMWH on placental HMGB1 modulation. Indeed, HMGB1 protein increase accompanied by decreased TNFα and IL-6 expression in LMWH villous explants confirm the anti-inflammatory effect of heparin and suggest that it is mediated by structural modifications of HMGB1 able to promote its accumulation and to inhibit its function. Further investigations are required.
International Federation of Placenta Associations (IFPA) meeting 2013
Whistler, CANADA
11-14 settembre 2013
34
41
41
Placenta; Preeclampsia; Low Molecular Weight Heparin; HMGB1
Cristian Zenerino;Anna Maria Nuzzo;Alessandra Zicari;Domenica Giuffrida;Tullia Todros;Alessandro Rolfo
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/142950
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? 0
social impact