CYP1A1, GSTT1, IL-6 and IL-8 transcription and IL-6 secretion on umbilical endothelial cells from hypertensive pregnant women: Preliminary results.

The impact of pregnancy hypertension in the offspring endothelia remains unknown. We evaluated the transcriptional expression of four genes that participate in the process of endothelial dysfunction using umbilical vein endothelial cell cultures (HUVEC) from healthy pregnant women (PW) and those with hypertensive disorders (HD). The cytochrome P450 1A1 (CYP1A1), gluthathione S-transferase subtype T1 (GSTT1), interleukin 6 (IL-6) and 8 (IL-8) mRNA and IL-6 protein levels were assessed. IL-6 and IL-8 transcripts were significantly reduced in HUVEC obtained from HD women. Our results suggest that a hypertensive environment in utero modifies the transcriptional expression of key inflammatory molecules in the newborn.

Effects of gestational hypertension and pre-eclampsia in mRNA expression of fibrinolysis genes in primary cultured human umbilical vein endothelial cells.

Hypertension disorders (HD) and pre-eclampsia (PRE) are leading causes of maternal deaths worldwide. PRE is associated with vascular endothelial dysfunction and with deregulation of the fibrinolysis pathway genes. Fibrinolysis is the fibrin clot hydrolysis process catalyzed by plasmin, a proteolytic enzyme formed from plasminogen. Plasminogen is cleaved by tissue-type (tPA) and urokinase-type (uPA) activators and inhibited by the plasminogen activator inhibitors type-1 (PAI-1) and type-2 (PAI-2). The whole process maintains blood hemostasis. This study aims to assess PAI-1, PAI-2, tPA and uPA mRNA expression in primary cultured human umbilical vein endothelial cells (HUVEC) isolated and cultured from healthy, HD and PRE women. Results show that PAI-1 and PAI-2 mRNA decreased in HD-HUVEC, whereas PAI-1 and uPA decreased in PRE-HUVEC cultures compared to control ones. Notably, the expression ratio between pro- and anti-fibrinolytic actors remained unchanged among the studied groups. It seems that newborn's hemostasis is maintained balanced probably by a compensatory mechanism that involves changes in the fibrinolysis gene expression profile. The real impact of these changes in mRNA expression is unknown, however, it is suggested that these changes could be associated with an increased predisposition to vascular disease development in the progeny.

Commercial single-walled carbon nanotubes effects in fibrinolysis of human umbilical vein endothelial cells.

Recent studies have demonstrated that carbon nanotubes (CNTs) induce platelet aggregation, endothelial dysfunction and vascular thrombosis. However, there is little information on the effects of CNTs on fibrinolysis. We investigated the role of pristine-commercial single-walled carbon nanotubes (SWCNTs) with <3% Co content in fibrinolysis and their contribution to the induction of pro-thrombotic processes in human vein endothelial cells (HUVEC). SWCNTs alone produced concentration-dependent oxidation, as measured by a dithiothreitol oxidation assay. Internalized SWCNTs were located in HUVEC treated with 25 µg/ml using transmission electron microscopy, whereas treatment with 50 µg/ml compromised cell viability, and oxidative stress increased significantly at 5 µg/ml. The study showed that in HUVEC treated with 25 µg SWCNT/ml, fibrinolysis-related gene expression and protein levels had increased by 3-12 h after treatment (serpine-1: 13-fold; PLAT: 11-fold and PLAU: 2-fold), but only the PAI-1 protein was increased (1.5-fold), whereas tissue and urokinase plasminogen activator proteins (tPA and uPA, respectively) tended to decrease. In summary, pristine SWCNTs treatment resulted in evident HUVEC damage caused by cell fiber contact, internalization, and oxidative stress due to contaminant metals. The generation of endothelial dysfunction, as shown by the altered expression of genes and proteins involved in fibrinolysis, suggest that SWCNTs display pro-thrombotic effects.

Mechanisms of toxicity by carbon nanotubes.

Carbon nanotubes (CNTs) consist of a family of carbon built nanoparticles, whose biological effects depend on their physical characteristics and other constitutive chemicals (impurities and functions attached). CNTs are considered the twenty first century material due to their unique physicochemical characteristics and applicability to industrial product. The use of these materials steadily increases worldwide and toxic outcomes need to be studied for each nanomaterial in depth to prevent adverse effects to humans and the environment. Entrance into the body is physical, and usually few nanoparticles enter the body; however, once there, they are persistent due to their limited metabolisms, so their removal is slow, and chronic cumulative health effects are studied. Oxidative stress is the main mechanism of toxicity but size, agglomeration, chirality as well as impurities and functionalization are some of the structural and chemical characteristic contributing to the CNTs toxicity outcomes. Among the many toxicity pathways, interference with cytoskeleton and fibrous mechanisms, cell signaling, membrane perturbations and the production of cytokines, chemokines and inflammation are some of the effects resulting from exposure to CNTs. The aim of this review is to offer an up-to-date scope of the effects of CNTs on biological systems with attention to mechanisms of toxicity.