scholarly journals The Protective Effect of Dabigatran and Rivaroxaban on DNA Oxidative Changes in a Model of Vascular Endothelial Damage with Oxidized Cholesterol

2020 ◽  
Vol 21 (6) ◽  
pp. 1953 ◽  
Author(s):  
Ewelina Woźniak ◽  
Marlena Broncel ◽  
Bożena Bukowska ◽  
Paulina Gorzelak-Pabiś
Keyword(s):  
Oxidative Damage ◽  
Oxidative Dna Damage ◽  
Vascular Endothelial Cells ◽  
Endothelial Damage ◽  
Vascular Endothelial ◽  
Coronary Syndrome ◽  
Oxidized Cholesterol ◽  
Endonuclease Iii ◽  
Single Strand Breaks ◽  
Repairing Effect

Background: Atherosclerotic plaques are unstable, and their release may result in thrombosis; therefore, currently, antiplatelet therapy with anticoagulants is recommended for the treatment of acute coronary syndrome. The aim of this study was to assess the effect of oxidized cholesterol on human umbilical vascular endothelial cells (HUVECs). The study also examines the protective and repairing effect of dabigatran and rivaroxaban in a model of vascular endothelial damage with 25-hydroxycholesterol (25-OHC). Methods: HUVECs were treated with compounds induce DNA single-strand breaks (SSBs) using the comet assay. Oxidative DNA damage was detected using endonuclease III (Nth) or human 8 oxoguanine DNA glycosylase (hOOG1). Reactive oxygen species (ROS) formation was determined using flow cytometry. Results: 25-hydroxycholesterol caused DNA SSBs, induced oxidative damage and increased ROS in the HUVECs; ROS level was lowered by dabigatran and rivaroxaban. Only dabigatran was able to completely repair the DNA SSBs induced by oxysterol. Dabigatran was able to reduce the level of oxidative damage of pyrimidines induced by oxysterol to the level of control cells. Conclusions: Observed changes strongly suggest that the tested anticoagulants induced indirect repair of DNA by inhibiting ROS production. Furthermore, dabigatran appears to have a higher antioxidant activity than rivaroxaban.

scholarly journals Clostridium perfringens Epsilon-Toxin Increases Permeability of Single Perfused Microvessels of Rat Mesentery

2005 ◽  
Vol 73 (8) ◽  
pp. 4879-4887 ◽  
Author(s):  
R. H. Adamson ◽  
J. C. Ly ◽  
M. Fernandez-Miyakawa ◽  
S. Ochi ◽  
J. Sakurai ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Clostridium Perfringens ◽  
Vascular Endothelial Cells ◽  
Intestinal Barrier ◽  
Endothelial Damage ◽  
Direct Access ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Rat Mesentery ◽  
Epsilon Toxin

ABSTRACT Epsilon-toxin, the primary virulence factor of Clostridium perfringens type D, causes mortality in livestock, particularly sheep and goats, in which it induces an often-fatal enterotoxemia. It is believed to compromise the intestinal barrier and then enter the gut vasculature, from which it is carried systemically, causing widespread vascular endothelial damage and edema. Here we used single perfused venular microvessels in rat mesentery, which enabled direct observation of permeability properties of the in situ vascular wall during exposure to toxin. We determined the hydraulic conductivity (Lp ) of microvessels as a measure of the response to epsilon-toxin. We found that microvessels were highly sensitive to toxin. At 10 μg ml−1 the Lp increased irreversibly to more than 15 times the control value by 10 min. At 0.3 μg ml−1 no increase in Lp was observed for up to 90 min. The toxin-induced increase in Lp was consistent with changes in ultrastructure of microvessels exposed to the toxin. Those microvessels exhibited gaps either between or through endothelial cells where perfusate had direct access to the basement membrane. Many endothelial cells appeared necrotic, highly attenuated, and with dense cytoplasm. We showed that epsilon-toxin, in a time- and dose-dependent manner, rapidly and irreversibly compromised the barrier function of venular microvessel endothelium. The results conformed to the hypothesis that epsilon-toxin interacts with vascular endothelial cells and increases the vessel wall permeability by direct damage of the endothelium.

scholarly journals Fluvastatin reduces oxidative damage in human vascular endothelial cells by upregulating Bcl-2

2008 ◽  
Vol 6 (4) ◽  
pp. 692-700 ◽  
Author(s):  
S. Z. XU ◽  
W. ZHONG ◽  
N. M. WATSON ◽  
E. DICKERSON ◽  
J. D. WAKE ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Oxidative Damage ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial

scholarly journals The role of neutrophils in the pathogenesis of atherosclerosis

2018 ◽  
Vol 17 (6) ◽  
pp. 110-116
Author(s):  
Yu. V. Saranchina ◽  
S. V. Dutova ◽  
O. Yu. Kilina ◽  
N. V. Khanarin ◽  
T. S. Kulakova
Keyword(s):  
Clinical Symptoms ◽  
Protein Complexes ◽  
Endothelial Damage ◽  
Current Data ◽  
Vascular Endothelial ◽  
Coronary Syndrome ◽  
Physiological Processes ◽  
Atherosclerotic Lesions ◽  
Structure And Functions

Atherosclerosis (AS) is one of the causes of cardiovascular disease. The formation of atherosclerotic lesions of the arteries is a long process, and clinical symptoms appear already at the stage of atherosclerotic plaque (ASB), which prevents blood flow and can cause coronary heart disease, as well as acute coronary syndrome. The study of atherosclerosis mechanisms at the subclinical level is relevant. This article provides a summary of current data on the structure and functions of neutrophils (NF) in physiological processes. Particular attention is paid to the participation of neutrophils in the damage and formation of vascular endothelial dysfunction. Discusses several mechanisms of involvement of neutrophils in atherogenesis: the production of reactive oxygen species, which cause direct endothelial damage; the synthesis of cytokines that trigger the migration of leukocytes in inflammation; the formation of protein complexes with cholesterol, contributing to their deposition in the vessels, and neutrophil traps, triggering destructive-alterative reactions.

scholarly journals Sinapine Thiocyanate Ameliorates Vascular Endothelial Dysfunction in Hypertension by Inhibiting Activation of the NLRP3 Inflammasome

2021 ◽  
Vol 11 ◽  
Author(s):  
Yang Liu ◽  
Hong-lin Yin ◽  
Chao Li ◽  
Feng Jiang ◽  
Shi-jun Zhang ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Nlrp3 Inflammasome ◽  
Vascular Endothelial Cells ◽  
Endothelial Damage ◽  
Endothelial Injury ◽  
Inflammasome Activation ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Nlrp3 Gene ◽  
Spontaneously Hypertensive

The increase of blood pressure is accompanied by the changes in the morphology and function of vascular endothelial cells. Vascular endothelial injury and hypertension actually interact as both cause and effect. A large number of studies have proved that inflammation plays a significant role in the occurrence and development of hypertension, but the potential mechanism between inflammation and hypertensive endothelial injury is still ambiguous. The purpose of this study was to explore the association between the activation of NLRP3 inflammasome and hypertensive endothelial damage, and to demonstrate the protective effect of sinapine thiocyanate (ST) on endothelia in hypertension. The expression of NLRP3 gene was silenced by tail vein injection of adeno-associated virus (AAVs) in spontaneously hypertensive rats (SHRs), indicating that activation of NLRP3 inflammasome accelerated hypertensive endothelial injury. ST not only protected vascular endothelial function in SHRs by inhibiting the activation of NLRP3 inflammasome and the expression of related inflammatory mediators, but also improved AngII-induced huvec injury. In summary, our results show that alleviative NLRP3 inflammasome activation attenuates hypertensive endothelial damage and ST ameliorates vascular endothelial dysfunction in hypertension via inhibiting activation of the NLRP3 inflammasome.

Klotho protein inhibits H2O2-induced oxidative injury in endothelial cells via regulation of PI3K/AKT/Nrf2/HO-1 pathways

2019 ◽  
Vol 97 (5) ◽  
pp. 370-376 ◽  
Author(s):  
Wei Cui ◽  
Bin Leng ◽  
GaoPin Wang
Keyword(s):  
Endothelial Cells ◽  
Oxidative Damage ◽  
Nuclear Translocation ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Heme Oxygenase 1 ◽  
Protective Mechanism ◽  
Vascular Endothelial ◽  
Necrosis Factor Alpha ◽  
Klotho Protein

Klotho protein secreted in the blood could act as a hormone to regulate various target organs and have a protective effect on the cardiovascular system. Numerous studies had shown that Klotho protein had antioxidative stress, anti-inflammatory, and antiapoptotic effects on vascular endothelial cells. The purpose of this study was to investigate the protective mechanism of Klotho protein on oxidative damage of vascular endothelial cells induced by H2O2. Klotho protein significantly enhanced human umbilical vein endothelial cells viability and increased the activities of antioxidant enzymes (superoxide dismutase, catalase, and heme oxygenase-1 (HO-1)), scavenged reactive oxygen species, and inhibited tumor necrosis factor alpha and interleukin 6 secretion. Klotho protein also reduced the rate of apoptosis of cells and improved the function of vascular endothelial cells (increased nitric oxide secretion). Klotho protein activated nuclear translocation of Nrf2 and increased HO-1 expression. Klotho protein also activated phosphorylation of protein kinase B (AKT), whereas the addition of LY294002, a pharmacological inhibitor of phosphatidylinositol 3-kinase (PI3K), blocked Klotho-protein-induced Nrf2/HO-1 activation and cytoprotection. Klotho protein enhanced the antioxidant defense ability of the cells by activating the PI3K/AKT pathway, which upregulated the expression of Nrf2/HO-1, thereby inhibiting H2O2-induced oxidative damage.

scholarly journals Mechanism of Vascular Endothelial Dysfunction Causing Arteriosclerosis: Vascular Endothelial Glycocalyx

2020 ◽  
Author(s):  
Minako Yamaoka-Tojo
Keyword(s):  
Endothelial Dysfunction ◽  
Vascular Endothelial Cells ◽  
Endothelial Glycocalyx ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Microvascular Angina ◽  
Coronary Syndrome ◽  
Acute Infectious Disease ◽  
Matrix Bound ◽  
Cell Lining

In atherosclerosis patients, vascular endothelial dysfunction is commonly observed with damage of vascular endothelial glycocalyx, an extracellular matrix-bound to and encapsulating the endothelial cell lining the blood vessel wall. Unfavorable lifestyle; smoking and physical inactivity, also induces glycocalyx degradation. Moreover, the vascular endothelial glycocalyx is damaged by various unfavorable disease conditions like as dehydration, acute infectious disease, trauma, sepsis, ARDS, Kawasaki disease, preeclampsia, gestational diabetes mellitus, hypertension, diabetes, chronic kidney disease, atherosclerosis, stroke, dementia, microvascular angina, acute coronary syndrome, and heart failure. The vascular endothelial glycocalyx has been shown to be important not only as a physical cytoprotective barrier for vascular endothelial cells but also as a mechanism that regulates intracellular cell signaling. Therefore, vascular endothelial glycocalyx has great potential to explore new strategies for assessing the benefit conditions of our healthy vasculature.

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