Mariana Bertozzi-Matheus

Preeclampsia (PE) is a gestational hypertensive disease characterized by endothelial dysfunction. Epigallocatechin-3-gallate (EGCG), the main compound in green tea, is a promising therapeutic target for the disease. By activating eNOS, EGCG increased NO production and exerted an important antioxidant action, but its specific impact in the context of PE remains understudied. The aim of this study is to evaluate the effects of EGCG on endothelial function in static and shear stress in in vitro models of PE. Endothelial cells were incubated with healthy (HP) and preeclamptic (PE) pregnant women’s plasma, and the latter group was treated with EGCG. Additionally, NOS (L-NAME) and PI3K protein (LY249002) inhibitors were also used. The levels of NO, ROS, and O2^•− were evaluated, as well as the antioxidant potential. These investigations were also carried out in a shear stress model. We found that EGCG increases the NO levels, which were reduced in the PE group. This effect was attenuated with the use of L-NAME and LY249002. Furthermore, EGCG increased the antioxidant capacity of PE, but its action decreased with LY294002. In cells subjected to shear stress, EGCG increased nitrite levels in the PE group and maintained its action on the antioxidant capacity. This is the first study of the effects of EGCG in this experimental model, as well as the investigation of its effects along with shear stress. Our findings suggest that EGCG improves parameters of endothelial dysfunction in vitro, making it a promising target in the search for treatments for the disease.

Preeclampsia (PE) is characterized by great endothelial dysfunction, decreased nitric oxide (NO) bioavailability, and higher levels of arginase activity. In the present study, we investigated the potential modulatory effects of trans-resveratrol (RSV) on arginase and endothelial dysfunction biomarkers in endothelial cells exposed to plasma from patients with PE and healthy pregnant (HP) women, and umbilical arteries from patients with PE. Human umbilical vein endothelial cells (HUVECs) were incubated with pooled plasma from 10 HP or 10 PE pregnant women and RSV; umbilical arteries from patients with PE were incubated with RSV; intracellular NO and total reactive oxygen species (ROS) levels were assessed using a probe that interacted with these radicals; total arginase activity was evaluated measuring the urea produced; total antioxidant capacity was measured using the ferric reduction ability power (FRAP) assay; and endothelial dysfunction biomarkers were assessed using qPCR in endothelial cells and umbilical arteries. RSV increased NO levels and decreased total arginase activity in endothelial cells incubated with plasma from patients with PE. In addition, RSV increased total antioxidant capacity and downregulated endothelial dysfunction biomarkers, such as intercellular adhesion molecule-1 (ICAM-1), von Willebrand factor (vWF), and Caspase-3, (CASP-3), in endothelial cells and umbilical arteries from PE patients. RSV treatment positively modulated the _L-arginine–NO pathway, decreased arginase activity, and increased antioxidant capacity, in addition to downregulating endothelial dysfunction biomarkers.

(1) Background: The bioavailability of nitric oxide (NO) and oxidative stress are important events related to the pathophysiology of preeclampsia (PE). In this present study, we aimed to evaluate the antioxidant effect of glibenclamide (GB) on the NO synthesis, oxidative stress, and antioxidant capacity in endothelial cells incubated with plasma from preeclamptic (PE) and normotensive pregnant women (NT). (2) Methods: Human umbilical vein endothelial cells (HUVECs) were incubated with a plasma pool from 10 NT and 10 PE pregnant women; NO/NOx quantification and ROS levels were assessed by a fluorescence compound; lipid peroxidation was evaluated employing thiobarbituric acid (TBA); and total antioxidant capacity was measured by ferric reduction ability power (FRAP) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). (3) Results: We found that endothelial cells incubated with plasma from PE showed lower NO and NOx levels compared with the NT group. However, GB treatment increased these levels, as well as the antioxidant capacity. Furthermore, a decrease was observed in ROS generation and lipid peroxidation (4) Conclusions: The GB treatment exerted a positive effect on the NO/NOx production by HUVEC incubated with plasma from NT and PE pregnant women, as well as in the reduction in oxidative stress and increase in the antioxidant capacity.

Background: Low bioavailability of nitric oxide (NO) is related to the pathophysiology of preeclampsia (PE). In the present study, we investigated the effect of nebivolol (NEB), a β₃-receptor agonist with vasodilator properties, on the NO synthesis in endothelial cells incubated with plasma from preeclamptic patients. Methods and results: Human umbilical vein endothelial cells (HUVECs) were incubated with plasma from healthy pregnant (HP) and PE women; NO quantification was assessed by a fluorescence compound. We found that endothelial cells incubated with plasma from women with PE show lower NO levels compared with the HP group (p < 0.0001). However, NEB treatment increases NO levels, partially, mediated by β₃ adrenergic receptors (p < 0.0001) and through eNOS activation (p < 0.0001). Conclusions: Our results suggest that NEB acts in NO synthesis through eNOS activation and β₃ adrenergic receptors in the endothelium. However, further studies will be needed to understand this molecule.