VEGF Deficit is Involved in Endothelium Dysfunction in Preeclampsia

This study examined the association of expression of vascular endothelial growth factor(VEGF),a promoter of angiogenesis,with endothelium dysfunction in preeclampsia.The level of VEGF protein and mRNA in the placenta and peripheral blood samples of 30 preeclampsia patients and 30 normotensive pregnant women was measured by immunohistochemistry,real-time reverse transcriptase-polymerase chain reaction(RT-PCR) and enzyme-linked immunosorbent assay(ELISA),respectively.VEGF expression in the human umbilical vein endothelial cells(HUVECs) was blocked by small interfering RNAs(siRNAs).The monolayer barrier function of HUVECs was determined by measuring the fluorescence intensity of BSA that crossed the HUVEC monolayers.The cell proliferation and cell-secreted nitric oxide(NO) level were detected by MTT method and nitrate reductase assay,respectively.The results showed that VEGF was expressed in the syncytiotrophoblasts and endothelial cells of vessels and capillaries in the placenta tissue.The serum level of VEGF in the preeclampsia patients was significantly decreased as compared with that in normal pregnant subjects,although VEGF mRNA expression in the placenta tissue of preeclampsia patients remained still high.Moreover,VEGF deficit could lead to endothelium cell dysfunction,and the administration of VEGF could protect endothelium cells from injury.It was concluded that lack of VEGF contributes to endothelium dysfunction,which may lead to the occurrence and development of preeclampsia.

Luteoloside protects the vascular endothelium against iron overload injury via the ROS/ADMA/DDAHⅡ/eNOS/NO pathway

Iron overload injury is considered to be a part of blood stasis syndrome of arthralgia in traditional Chinese medicine.Its primary therapies include clearing heat and detoxification,activating blood circulation,and removing blood stasis.Lonicera japonica flos(LJF)has long been known as an excellent antipyretic and antidote.Luteoloside(Lut)is one of the main components of LJF and exhibits antioxidant,anti-inflammatory,and cytoprotective properties.However,the protection of Lut against iron overload injury and its underlying mechanisms remain unclear.Therefore,HUVECs were exposed to 50μmol·L^(−1)iron dextran for 48 h to establish an iron overload damage model and the effects of Lut were assessed.Our results showed that 20μmol·L^(−1)Lut not only increased cell viability and weakened LDH activity,but also significantly up-regulated DDAHⅡexpression and activity,increased p-eNOS/eNOS ratio and NO content,and reduced ADMA content in HUVECs exposed to iron overload.Furthermore,Lut significantly attenuated intracellular/mitochondrial ROS generation,improved SOD,CAT,and GSH-Px activities,reduced MDA content,maintained MMP,inhibited mPTP opening,prevented cyt c from mitochondria released into cytoplasm,reduced cleaved-caspase3 expression,and ultimately decreased cell apoptosis induced by iron overload.The effects of Lut were similar to those of L-arginine(an ADMA competitive substrate),cyclosporin A(a mPTP blocker agent),and edaravone(a free radical scavenger)as positive controls.However,addition of pAD/DDAHⅡ-shRNA adenovirus reversed the above beneficial effects of Lut.In conclusion,Lut can protect HUVECs against iron overload injury via the ROS/ADMA/DDAHⅡ/eNOS/NO pathway.The mitochondria are the target organelles of Lut’s protective effects.