Disseminated intravascular coagulation in an ambulatory young woman

We are reporting the case of an ambulatory young woman with a 10-year history of recurrent venous thrombosis who presented to us with diffuse intravascular coagulation (DIC). After excluding the recognized causes of DIC, we examined the possibility that her clinically quiescent ulcerative colitis might be the underlying stimulus. We documented sepsis-range endotoxemia in this patient at a time when she was afebrile and had a normal C-reactive protein level. In vitro her serum upregulated tissue factor in cultured endothelial cells. We postulate that she had become tolerant to the systemic effects of endotoxin leaking from her inflamed colon but that the endotoxin stimulated her endothelium and/or monocytes to produce tissue factor that made her intensely hypercoagulable. Her prothrombotic state may have been compounded by the fact that she was heterozygous for prothrombin G20210A and that her plasma clotting time demonstrated resistance to activated protein C.     

Inostamycin suppresses vascular endothelial growth factor-stimulated growth and migration of human umbilical vein endothelial cells

Angiogenesis involves multiple steps including proliferation and migration of endothelial cells. In the present study, we determined the effect of inostamycin (an inhibitor of phosphatidylinositol synthesis) on vascular endothelial growth factor (VEGF)-induced proliferation and migration of human umbilical vein endothelial cells (HUVECs). Inostamycin significantly attenuated both VEGF-induced proliferation and migration of HUVECs. Inostamycin inhibited activation of mitogen-activated kinases (ERK and p38) and elevation of cyclin D1 induced by VEGF. These data suggest that inostamycin reduced both proliferation and migration of HUVECs by targeting ERK-cyclin D1 and p38, respectively.     

Cytotoxicity,oxidative stress and inflammation induced by ZnO nanoparticles in endothelial cells: interaction with palmitate or lipopolysaccharide

Recent studies showed that ZnO nanoparticles (NPs) might induce the toxicity to human endothelial cells. However, little is known about the interaction between ZnO NPs and circulatory components, which is likely to occur when NPs enter the blood. In this study, we evaluated ZnO NP‐induced cytotoxicity, oxidative stress and inflammation in human umbilical vein endothelial cells (HUVECs), with the emphasis on the interaction with palmitate (PA) or lipopolysaccharide (LPS), because PA and LPS are normal components in human blood that increase in metabolic diseases. Overall, ZnO NPs induced cytotoxicity and intracellular reactive oxygen species (ROS) at a concentration of 32 μg ml⁻¹, but did not significantly affect the release of inflammatory cytokines or adhesion of THP‐1 monocytes to HUVECs. In addition, exposure to ZnO NPs dose‐dependently promoted intracellular Zn ions in HUVECs. PA and LPS have different effects. Two hundred μm PA significantly induced cytotoxicity and THP‐1 monocyte adhesion, but did not affect ROS or release of inflammatory cytokines. In contrast, 1 μg ml⁻¹ LPS significantly induced ROS, release of inflammatory cytokines and THP‐1 monocyte adhesion, but not cytotoxicity. The presence of ZnO NPs did not significantly affect the toxicity induced by PA or LPS. In addition, the accumulation of Zn ions after ZnO NP exposure was not significantly affected by the presence of PA or LPS. We concluded that there was no interaction between ZnO NPs and PA or LPS on toxicity to HUVECs in vitro . Copyright © 2016 John Wiley & Sons, Ltd.     

Anti-Vascular Inflammatory Effect of Ethanol Extract from Securinega suffruticosa in Human Umbilical Vein Endothelial Cells

Securiniga suffruticosa is known as a drug that has the effect of improving the blood circulation and relaxing muscles and tendons, thereby protects and strengthen kidney and spleen. Therefore, in this study, treatment of Securiniga suffruticosa showed protective effect of inhibiting the vascular inflammation in human umbilical vein endothelial cells (HUVECs) by inducing nitric oxide (NO) production and endothelial nitric oxide synthase (eNOS) coupling pathway. In this study, Securiniga suffruticosa suppressed TNF-α (Tumor necrosis factor–α) induced protein and mRNA levels of cell adhesion molecules such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and Interleukin-6 (IL-6). Pretreatment of HUVEC with Securiniga suffruticosa decreased the adhesion of HL-60 cells to Ox-LDL (Oxidized Low-Density-Lipoprotein)-induced HUVEC. Moreover, Securiniga suffruticosa inhibited TNF-α induced intracellular reactive oxygen species (ROS) production. Securiniga suffruticosa also inhibited phosphorylation of IκB-α in cytoplasm and translocation of NF-κB (Nuclear factor-kappa B) p65 to the nucleus. Securiniga suffruticosa increased NO production, as well increased the phosphorylation of eNOS and Akt (protein kinase B) which are related with NO production. In addition, Securiniga suffruticosa increased the protein expression of GTPCH (Guanosine triphosphate cyclohydrolase Ⅰ) and the production of BH4 in HUVEC which are related with eNOS coupling pathway. In conclusion, Securiniga suffruticosa has a protective effect against vascular inflammation and can be a potential therapeutic agent for early atherosclerosis.     

洛铂和顺铂对血管内皮细胞及肝、肾细胞损伤的体外实验研究

目的分析洛铂（LBP）和顺铂（DDP）对传代培养的人脐静脉内皮细胞株（HUVECs）、人肝细胞株（QSG-7701）和人近端肾小管上皮细胞（HK-2细胞）的抑制作用,并初步探讨其可能机制。方法采用MTT法检测LBP和DDP对HUVECs、QSG-7701和HK-2细胞抑制作用的差异,并测定HK-2细胞培养液中丙二醛（MDA）和超氧化物歧化酶（SOD）含量,观察LBP和DDP对HK-2细胞脂质过氧化过程的影响。结果在相同浓度、相同作用时间下,DDP组对HK-2细胞抑制率明显高于LBP组（P〈0.05）,而LBP组对HUVECs细胞的抑制率明显高于DDP组（P〈0.05）;LBP组和DDP组对QSG-7701抑制率的差异无统计学意义（P〉0.05）;此外,与空白对照组比较,LBP组和DDP组均使HK-2细胞培养液中MDA含量明显升高,SOD活性明显降低（P均〈0.05）,但LBP组和DDP组间差异无统计学意义（P〉0.05）。结论 LBP和DDP均对肝、肾细胞有较强的抑制作用,LBP的肾细胞毒性较DDP低,LBP组对正常人脐静脉内皮细胞抑制作用明显强于DDP组,提示LBP可能具有更强的抑制血管形成的能力;氧化性损伤可能是两者造成肾毒性的机制。     

二甲双胍调节内皮细胞组织因子途径抑制物的表达

<正>组织因子途径抑制物(tissue factor pathway inhibitor,TF-PI)高表达于血管内皮细胞表面,特异性抑制外源性凝血途径,是一种控制凝血启动的抗凝蛋白[1]。血栓形成是糖尿病的主要并发症之一。糖尿病患者血糖持续升高,导致糖基化终末产物(advanced glycosylation end products,AGEs)的生成[2]。AGEs水平可上调组织因子,促进血栓形成。作为控     

Screening and evaluation of traditional Chinese medicine by microarray expression analysis

Ethnopharmacological relevance

Salvia miltiorrhiza is a Chinese medicinal herb, which is widely used for the treatment of cardiovascular disorders. In this article, we investigated the effects of Salvia miltiorrhiza and its hydrophilic and lipophilic components (HCS and LCS) on human umbilical vein endothelial cells (HUVECs), and the molecular mechanism was explored by microarray gene expression profiling.

Materials and methods

Cell proliferation and migration were used to evaluate the angiogenic effects of HCS, LCS and total extract of Salvia miltiorrhiza (TES). Microarray technology was applied to detect the gene expression of HUVECs treated with TES, HCS and LCS. Besides, quantitative real-time PCR was used to verify the microarray results.

Results

Our results showed that LCS inhibited the proliferation and migration of HUVECs, HCS promoted the proliferation and migration of HUVECs, and TES did not affect the viability of HUVECs at the concentration of 5 µg/mL. From the result of principle component analysis (PCA) of microarray data, the effect of LCS on HUVECs was significantly different from the other components. Moreover, there were more differentially expression genes in LCS group than in the other groups, which meant LCS had a strong influence on HUVECs. Compared with untreated cells, 511 significantly changed genes had been detected in LCS treated cells and 236 (approximately 46%) of them were up-regulated. The mRNA expression of IL-6 was found to be increased significantly in LCS group.

Conclusions

In Salvia miltiorrhiza, HCS and LCS had opposite effects on HUVECs. LCS showed significantly inhibitory action on HUVECs proliferation and migration. It was proposed that LCS could apply in the diseases caused by vascular anomaly hyperplasia. In the mechanism of action of LCS on HUVECs, the pathways of ErbB, MAPK, p53, oxidative phosphorylation and inflammatory response were involved.     

蓬子菜总黄酮对过氧化氢损伤的人脐静脉内皮细胞的保护作用

目的:探讨蓬子菜总黄酮对人脐静脉内皮细胞(human umbilical vein endothelial cells,HU-VECs)的保护及损伤修复的作用。方法:采用台盼蓝染色法,观察不同剂量蓬子菜总黄酮(12.5～400μg.mL-1)对HUVECs生长的影响;建立过氧化氢(H2O2)诱导HUVECs氧化损伤模型,采用MTT比色法检测细胞增殖,酶联免疫分析方法检测内皮素-1(endothelin,ET-1)和降钙素基因相关肽(calcitonin generelated peptide,CGRP)的分泌水平。AO/EB双染色法观察HUVECs的凋亡。结果:与模型组比较,蓬子菜总黄酮能减轻H2O2对HUVECs增殖抑制作用,促进CGRP的分泌,降低ET-1的分泌水平,抑制HUVECs的凋亡。结论:蓬子菜总黄酮对氧化损伤的HUVECs具有保护及修复作用,其机制与调节ET-1和CGRP的分泌有关。     

Inhibition of ceramide synthesis reverses endothelial dysfunction and atherosclerosis in streptozotocin-induced diabetic rats

Objectives

To explore the effect of myriocin on EDVD and atherosclerosis in diabetic rats.

Methods

Rats were fed with a high-fat/high-sucrose/high-cholesterol diet (20% sucrose, 10% animal oil, 1.0% bile salt and 2.5% cholesterol) (hereinafter defined as diabetic groups) or Purina Rodent Chow (NC group), the former was intervened with low dose streptozotocin (30 mg/kg) after feeding 1 month to make diabetic model. The NC group was intervened with citrate buffer and the diabetic rats were intervened with myriocin (0.3 mg/kg Qod) (MTD group) or just solvent (DC group) for 14 weeks. The EDVD, thickness of fatty deposition under endothelium, ceramide, PI3K/PKB/eNOS, NO and other vital parameters were measured after the rats sacrificed.

Results

In DC group, the ceramide contents in serum and aorta increased, the EDVD was impaired, the fatty deposition under endothelium increased, and the phosphorylation of PI3K/PKB/eNOS and NO release decreased all compared with the NC group (P < 0.05). Compared with the DC group, the ceramide contents in MTD group decreased, the EDVD ameliorated, the fatty deposition diminished, and PI3K/PKB/eNOS phosphorylation and NO release (P < 0.05) increased.

Conclusions

After treated with myriocin, the EDVD in diabetic rats has been improved by increasing PI3K/PKB/eNOS phosphorylation and NO release, and meanwhile the atherosclerosis has reversed.     

The effects of cadmium on VEGF-mediated angiogenesis in HUVECs

Cadmium (Cd) is a highly toxic element that causes morphologic alterations and dysfunction in blood vessels. The altered vascular function caused by cadmium has been implicated in a range of chronic diseases, including hypertension. The effects of cadmium are a multisystem phenomenon involving inflammation, hypertrophy, apoptosis, angiogenesis and important processes involved in vascular remodeling systems. Vascular endothelial growth factor (VEGF) plays a major role in cell growth and angiogenesis under pathologic conditions. VEGF secretion is related to anti-apoptosis protein expression and attenuates apoptosis in endothelial cells. This study examined the VEGF-dependent mechanisms of angiogenesis and apoptosis in cadmium-treated endothelial cells (HUVECs). The effects and mechanisms of cadmium in endothelial cells (HUVECs) were examined by exposing the cells to different doses of cadmium chloride (2.5-40 μ m). After the cadmium treatment, the angiogenesis and apoptosis mechanisms related to VEGF in cadmium-treated HUVECs were examined. As a result, the low concentration of cadmium increased the tube formation in HUVECs. In addition, cadmium at concentrations of 5 and 10 μ m increased VEGF secretion and VEGFR2 activity, which suggest that cadmium affects the growth of blood vessels. All three MAPK pathways, namely ERK, JNK and p38, were activated by cadmium in HUVECs. However, high concentrations of cadmium caused cell damage, disrupted tube formation and inhibited VEGF expression and the activities of VEGFR2 and MAPK in HUVECs. Cadmium has dual functions through VEGF-dependent mechanisms in a dose-dependent manner. In this study, the dual effects of cadmium might alter angiogenesis and induce apoptosis through VEGF pathways in HUVECs.