scholarly journals Cholesterol crystals of atherosclerotic lesions induce endothelial dysfunction via RhoA activation

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Yvonne Baumer ◽  
Svenja Meiler ◽  
Pavlos Anastasiadis ◽  
John Allen ◽  
William A. Boisvert
Keyword(s):  
Endothelial Dysfunction ◽  
Cholesterol Crystals ◽  
Rhoa Activation ◽  
Atherosclerotic Lesions

scholarly journals State-of-the-Art Review: Endothelial Dysfunction in the Pathogenesis of Atherosclerosis

2001 ◽  
Vol 7 (4) ◽  
pp. 276-280 ◽  
Author(s):  
Pavel Poredoš
Keyword(s):  
Risk Factors ◽  
Endothelial Dysfunction ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Common Denominator ◽  
Atherosclerotic Lesions ◽  
Circulating Markers ◽  
Thrombotic Complications ◽  
Atherosclerotic Process ◽  
Von Willebrand

Healthy endothelium plays a central role in cardiovascular control. Therefore, endothelial dysfunction (ED), which is characterized by an imbalance between relaxing and contracting factors, procoagulant and anticoagulant substances, and between proinflammatory and antiinflammatory mediators, may play a particularly significant role in the pathogenesis of atherosclerosis. Endothelial dysfunction is closely related to different risk factors of atherosclerosis, and to their intensity and duration. The involvement of risk factors in ED is also supported by results of interventions studies that showed regression of ED with treatment of risk factors. Because risk factors are commonly accompanied by decreased bioavailability of nitric oxide, the common denominator whereby different risk factors cause ED is most probably increased oxidative stress. Endothelial dysfunction may promote atherogenesis through different mechanisms such as increased adherence of monocytes, macrophages, and enhanced permeability of the endothelial layer. Further, ED probably plays an important role in the growth of atherosclerotic lesions and in the development of thrombotic complications in late stages of the disease. Because ED is a key underlying factor in the atherosclerotic process, markers of endothelial abnormalities have been sought. Detection of ED is based on tests of endothelium-dependent vasomotion (dilation capability of peripheral and coronary arteries) and on circulating markers of endothelial function (endothelin-1, von Willebrand factor, tissue plasminogen activator, plasminogen activator inhibitor, and adhesion molecules). Using these tests it is possible to follow the dose response of harmful effects of risk factors, and the effects of preventive procedures on vessel wall function.

scholarly journals Activation of NLRP3 inflammasome by cholesterol crystals in alcohol consumption induces atherosclerotic lesions

2017 ◽  
Vol 62 ◽  
pp. 291-305 ◽  
Author(s):  
P.M. Abdul-Muneer ◽  
Saleena Alikunju ◽  
Vikas Mishra ◽  
Heather Schuetz ◽  
Adam M. Szlachetka ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Nlrp3 Inflammasome ◽  
Cholesterol Crystals ◽  
Atherosclerotic Lesions

Abstract 1732: Deletion of Fc Receptor Ameliorates Progression of Atherosclerotic Lesions in LDL Receptor Knockout Mice: Protective Role against Vascular Inflammation and Oxidative Stress

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Katsuhiko Sumiyoshi ◽  
Kazunori Shimada ◽  
Takafumi Iesaki ◽  
Tetsuro Miyazaki ◽  
Atsumi Kume ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Vascular Inflammation ◽  
Ldl Receptor ◽  
Superoxide Production ◽  
High Cholesterol Diet ◽  
Vascular Endothelial ◽  
High Cholesterol ◽  
Atherosclerotic Lesions ◽  
Oil Red O Staining ◽  
Oil Red O

Background : Vascular endothelial dysfunction through the production of reactive oxygen species (ROS) plays an important role in the initiation and progression of atherosclerosis. Immunoglobulin Fc receptor (FcR) involves the activation of immune and inflammatory reaction, however, the role of FcR in endothelial function, ROS production, and atherogenesis, has not clearly elucidated. To examine the hypothesis that FcR deletion blunts the progression of atherosclerotic lesions via improvements of superoxide production and endothelial dysfunction, we generated FcR/LDL receptor double-knockout (DKO) mice. Methods : Mice (8 weeks) with LDL receptor knockout (LDLR-KO) and DKO were fed a high cholesterol diet for 10 weeks. We examined the endothelium-dependent relaxation of isolated thoracic aorta, superoxide production by dihydroethidium-derived fluorescence (DHE) staining before and after high cholesterol feeding. We also assessed atherosclerotic lesions by Oil Red O-staining, macrophage infiltration, and p22phox expression by immnohistochemical analysis. Results : Vascular endothelial-dependent relaxation induced by high cholesterol diet was significantly higher in DKO mice than in LDLR-KO mice (−53 ± 7% vs −22 ± 9, p < 0.05). Superoxide production was significantly lower in DKO mice than in LDLR-KO mice (13.6 ± 10 vs 38.8 ± 20 ×10 3 μ m 2 p < 0.05). The expression of p22phox in DKO mice was significantly lower than in LDLR-KO mice (90 ± 19 vs 141 ± 42 × 10 3 μm 2 p < 0.05). The area of macrophage infiltration of the vascular wall was significantly lower in DKO mice than LDLR-KO mice (34 ± 5 vs 59 ± 17 × 10 3 μ m 2 p < 0.05). The Oil -Red O staining showed the significant reduction of atherosclerotic lesions in DKO mice than in LDLR-KO mice (73 ± 24 vs 133 ± 31 × 10 4 μ m 2 p < 0.005). Conclusion : Deletion of FcR attenuated the production of ROS, vascular inflammation, and endothelial dysfunction, resulting in prevention of atherosclerotic formation in LDLR-KO mice. These data suggested that FcR might be involved in atherosclerotic process through not only vascular inflammation, but also oxidative stress in vasculature.

scholarly journals MECHANISMS OF ATHEROGENESIS AND ITS INTENSIFICATION IN PATIENTS WITH RHEUMATOID ARTHRITIS

2020 ◽  
pp. 8-24
Author(s):  
V. K. Kazymyrko ◽  
L. N. Ivanitska ◽  
T. S. Silantyeva ◽  
A. G. Dubkova ◽  
V. V. Kutovoy
Keyword(s):  
Immune Complexes ◽  
Protein Complexes ◽  
Cell Damage ◽  
Cholesterol Crystals ◽  
Atherosclerotic Lesions ◽  
Arterial Lesions ◽  
Tnf Α ◽  
Traditional Risk Factors ◽  
Mechanisms Of Development

The article describes the role of cholesterol crystals (CS) in the mechanisms of development in the inner lining of arteries of inflammation – granulomatosis, induced by foreign bodies. The smallest CS crystals are found already in early atherosclerotic lesions. They are a factor in the initiation and exacerbation of atherosclerosis (At), cause cell damage and apoptosis. The formation of crystals within the necrotic nuclei of plaques can lead to an increase in their volume and to rupture. It has been shown that damage to the membranes of macrophages phagolysosomes by absorbed CS crystals leads to the inclusion of protein complexes – inflammasomes – in the inflammatory process, which trigger the inflammatory signaling cascade and are responsible for the secretion of pro-inflammatory cytokines. Inflammasomes NLRP3 are necessary for the process of atherogenesis; their activation is a link between the metabolism of cholesterol and inflammation involving macrophages. Unlike At, RA is manifested by autoimmune inflammation and immunocomplex vasculitis. When these diseases are combined, the effects of proinflammatory cytokines add up, an increase in the severity of inflammation, increased tissue damage and progression of atherosclerotic arterial lesions. The accelerated development of At in RA patients is facilitated by a combination of the action of traditional risk factors for atherogenesis and damage to the walls (endothelium) of arteries by immune complexes, complement, neutrophils and lymphocytes with an increase in their permeability to the lipid factor. The deposition of immune complexes in the capillaries of plaques leads to damage to their walls, destabilization of plaques and the development of acute cardiovascular events. The intensification of lipid accumulation and inflammation in the plaques of RA patients is confirmed in the section. Anticytokine drugs, primarily TNF-α and IL-1β antagonists, are pathogenetically substantiated agents for the progression of At in patients with RA. Statins remain a widely used class of drugs. They, in addition to hypolipidemic, immunomodulatory and anti-inflammatory effects, affect the crystallization of cholesterol, dissolve crystals and stabilize plaques.

GPER inhibits diabetes-mediated RhoA activation to prevent vascular endothelial dysfunction

2016 ◽  
Vol 95 (2) ◽  
pp. 100-113 ◽  
Author(s):  
Zilin Li ◽  
Liang Cheng ◽  
Hongliang Liang ◽  
Weixun Duan ◽  
Jing Hu ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Rhoa Activation

Emulating endothelial dysfunction by implementing an early atherosclerotic microenvironment within a microfluidic chip

Lab on a Chip ◽  
2019 ◽  
Vol 19 (21) ◽  
pp. 3664-3677 ◽  
Author(s):  
Yujin Shin ◽  
Seongjin Lim ◽  
Jinwon Kim ◽  
Jessie S. Jeon ◽  
Hongki Yoo ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Microfluidic Chip ◽  
Micro Channel ◽  
Atherosclerotic Lesions ◽  
And Function

The pathophysiological phenotype and function of endothelial cells (ECs) in atherosclerotic lesions are replicated within a micro-channel by mimicking the microenvironment of the lesions.

scholarly journals Endothelial dysfunction in patients with hypertension and peripheral artery disease

2016 ◽  
Vol 97 (5) ◽  
pp. 691-695 ◽  
Author(s):  
M N Denisenko ◽  
V V Genkel ◽  
I I Shaposhnik
Keyword(s):  
Essential Hypertension ◽  
Endothelial Dysfunction ◽  
Peripheral Artery Disease ◽  
Brachial Artery ◽  
Lower Limb ◽  
Carotid Arteries ◽  
Peripheral Artery ◽  
Brachial Artery Diameter ◽  
Atherosclerotic Lesions ◽  
Artery Disease

Aim. To assess endothelial function in patients with hypertension and peripheral artery disease.Methods. The study included 100 patients with an established diagnosis of essential hypertension. Ultrasonic duplex scanning of brachiocephalic arteries and lower limb arteries was performed. The functional state of the endothelium was evaluated using postocclusive reactive hyperemia test by D.S. Celermajer.Results. Atherosclerotic plaques in the carotid arteries were found in 71% of patients, in the lower limb arteries - in 60%. The combined affection of both vascular beds was diagnosed in 51% of patients. Endothelial dysfunction was found in 64% of patients. In patients with carotid arterial system atherosclerosis, brachial artery dilation response was 6.1%, while in those with intact carotid arteries - 4.7% (p=0.041). The value of the brachial artery dilation response in patients with atherosclerotic lesions of lower extremities arteries was 5.9%. In the subgroup of patients with intact lower limbs arteries, the increase in brachial artery diameter was 9.60% an average (p=0.04). Among 51 people with affection of both vascular systems the brachial artery diameter increase was 5.4%, while in comparison, in the subgroup consisting of 49 patients without combined carotid and lower limb arteries lesions, - 9.9% (p=0.003). According to the results of the correlation analysis, the relation between endothelial dysfunction and the maximum percentage of stenosis of the carotid arteries and lower limb arteries at the level of tibial segment was revealed.Conclusion. In patients with hypertension and peripheral artery disease, decrease in dilation response in endothelium-dependent vasodilation test was registered regardless of the localization of atherosclerotic lesions; endothelial dysfunction in essential hypertension was associated with the highest percentage of stenosis of the carotid arteries and lower limb arteries at the level of tibial segment.

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