The Effect Of CORM-2on TM And EPCR Expression Of LPS-induced HUVEC And Mice

Objective: To observe the counter-effect of CORM-2on LPS-suppressed TM andEPCR expressions from HUVEC and c57bl/6mice, and to reveal its possiblemechanisms.Methods: HUVECs and thirty c57bl/6mice were divided into five treatment groupsrespectively, where reagents were added simultaneously: Control (negative control),LPS (positive control), CORM-2, CORM-2+LPS, and iCORM-2+LPS. TM andEPCR proteins of the cells and the culture medium levels of sTM, sEPCR andMMP-2were detected8h,16h yand24h after administration, while mRNA levels ofTM and EPCR, as well as NF-κB activity among groups was also evaluated at16h.TM and EPCR proteins of the lung of the mice and the plasma levels of sTM, sEPCRwere detected8h after administration.Results: No significant difference was observed in any indicator between CORM-2and Control groups. Addition of LPS produced drastic increase in MMP-2expression,NF-κB activity, shedding of TM and EPCR (into the culture medium and plasma), aswell as remarkable decrease in both mRNA and protein expressions of TM and EPCR,and cell viability. LPS+CORM-2treatment significantly reduced the increase inMMP-2, NF-κB activity, and TM/EPCR shedding, while maintained both mRNA andprotein levels of TM and EPCR, preserved cell viability. However when iCORM-2was used in the iCORM-2+LPS group, these protective effects was not observed.Conclusions: CORM-2protects HUVEC and mice from LPS induced injury, by wayof suppressing NF-κB activity, which down-regulates TM and EPCR mRNAs. It alsodecreases MMP-2expression and prevents the shedding of TM and EPCR from thesurface of endothelial cells, so as to preserve their protective effect.