BACKGROUND: The endothelial cell (EC) protein C receptor (EPCR) negatively regulates coagulation and inflammation. Factors and mechanisms regulating the expression of cell-bound EPCR and the release of soluble (s) EPCR are still unclear. METHODS: We investigated the reciprocal regulation of membrane-bound and sEPCR upon inflammation using primary cultures of vascular EC. The impact of 2 parameters, gender and EPCR gene A3 haplotype, on sEPCR plasma basal level and endothelial expression was examined by Elisa and flow cytometry. RESULTS: Exposure of EC to tumor necrosis factor α causes a rapid downregulation of membrane-associated EPCR expression without affecting markedly the spontaneous release of sEPCR by EC. In a cohort of 100 healthy donors, we show that males express significantly higher basal sEPCR in plasma than females (194 ± 12 vs. 145 ± 9 ng/ml, respectively, p<0.01). Both gender and EPCR A3 haplotype affect sEPCR plasma levels but have no apparent effect on EPCR expression by EC. No quantitative correlation between cellular expression and circulating blood sEPCR was observed, suggesting that endothelial expression may not reflect the plasma level. CONCLUSION: Male gender is another parameter with A3 haplotype associated with elevated sEPCR levels in blood, and both parameters may contribute to selective regulatory mechanisms of EPCR release upon inflammation.
BACKGROUND: The endothelial cell (EC) protein C receptor (EPCR) negatively regulates coagulation and inflammation. Factors and mechanisms regulating the expression of cell-bound EPCR and the release of soluble (s) EPCR are still unclear. METHODS: We investigated the reciprocal regulation of membrane-bound and sEPCR upon inflammation using primary cultures of vascular EC. The impact of 2 parameters, gender and EPCR gene A3 haplotype, on sEPCR plasma basal level and endothelial expression was examined by Elisa and flow cytometry. RESULTS: Exposure of EC to tumor necrosis factor α causes a rapid downregulation of membrane-associated EPCR expression without affecting markedly the spontaneous release of sEPCR by EC. In a cohort of 100 healthy donors, we show that males express significantly higher basal sEPCR in plasma than females (194 ± 12 vs. 145 ± 9 ng/ml, respectively, p<0.01). Both gender and EPCR A3 haplotype affect sEPCR plasma levels but have no apparent effect on EPCR expression by EC. No quantitative correlation between cellular expression and circulating blood sEPCR was observed, suggesting that endothelial expression may not reflect the plasma level. CONCLUSION: Male gender is another parameter with A3 haplotype associated with elevated sEPCR levels in blood, and both parameters may contribute to selective regulatory mechanisms of EPCR release upon inflammation.
Authors: Vijayalakshmi Sridharan; Kristin A Johnson; Reid D Landes; Maohua Cao; Preeti Singh; Gail Wagoner; Abdallah Hayar; Emily D Sprick; Kayla A Eveld; Anusha Bhattacharyya; Kimberly J Krager; Nukhet Aykin-Burns; Hartmut Weiler; Jose A Fernández; John H Griffin; Marjan Boerma Journal: PLoS One Date: 2021-05-24 Impact factor: 3.240
Authors: Helle Holm Hansson; Louise Turner; Line Møller; Christian William Wang; Daniel T R Minja; Samwel Gesase; Bruno Mmbando; Ib Christian Bygbjerg; Thor G Theander; John P A Lusingu; Michael Alifrangis; Thomas Lavstsen Journal: Malar J Date: 2015-12-01 Impact factor: 2.979