Interaction of endothelial cells and fibroblasts with modified fibrin networks: role in atherosclerosis

Shats, E.A.; Nair, C.H.; Dhall, D.P.

doi:10.1016/s0021-9150(96)06003-0

Cited by 31 publications

(18 citation statements)

References 16 publications

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“…VWF is the main determinant of factor VIII plasma levels (FVIII) [42] while FVIII is associated with CLT and risk of VTE [43]. It has been shown that fibrin network composed of thin fibres induces a less profibrinolytic environment in cultures of endothelial cells and fibroblasts than fibrin network composed of thick fibres, and thinner fibrin fibers cause endothelial cells to increase synthesis of vWF [44]. There have also been previous studies showing increased vWF levels in LA, coronary sinus and peripheral blood samples in patients with PsAF.…”

Section: Discussionmentioning

confidence: 99%

Denser plasma clot formation and impaired fibrinolysis in paroxysmal and persistent atrial fibrillation while on sinus rhythm: Association with thrombin generation, endothelial injury and platelet activation

Drabik¹,

Wołkow²,

Undas³

2015

Thrombosis Research

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Section: Discussionmentioning

confidence: 99%

Denser plasma clot formation and impaired fibrinolysis in paroxysmal and persistent atrial fibrillation while on sinus rhythm: Association with thrombin generation, endothelial injury and platelet activation

Drabik¹,

Wołkow²,

Undas³

2015

Thrombosis Research

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“…5,6,32,33 They proliferate in arterial wall and are the main source of extracellular matrix that causes the progressive fibrosis of the plaque. Furthermore, they participate in activation of endothelial cells and recruitment of leukocytes.…”

Section: Discussionmentioning

confidence: 99%

Enhanced P2X₇Activity in Human Fibroblasts From Diabetic Patients

Solini

Chiozzi

Morelli

et al. 2004

ATVB

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Objective-We have investigated expression and function of the P2X 7 receptor in fibroblasts from healthy subjects and patients with type 2 diabetes. Methods and Results-Fibroblasts were isolated from skin biopsies. P2X 7 receptor expression in both cell populations was measured by functional assays, RT-PCR, fluorescence-activated cell sorter, and immunoblotting. We found that fibroblasts from diabetic subjects are characterized by enhanced P2X 7 -mediated responses as indicated by increased shape changes, microvesiculation, enhanced fibronectin and interleukin 6 secretion, and accelerated apoptosis. These responses were blocked by preincubation with the P2X blockers KN-62, oxidized ATP, or pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid). Furthermore, we also found a higher level of spontaneous fibronectin secretion and of apoptosis in fibroblasts from diabetic compared with healthy subjects. Both higher basal level of fibronectin secretion and spontaneous rate of apoptosis were likely attributable to the increased pericellular concentration of ATP because fibroblasts from diabetic subjects released 3ϫ as much ATP into the supernatants compared with fibroblasts from healthy subjects. Conclusions-We conclude that fibroblasts from type 2 diabetes patients are characterized by a hyperactive purinergic loop based either on a higher level of ATP release or on increased P2X 7 reactivity. (Arterioscler Thromb Vasc Biol. 2004;24:1240-1245.)Key Words: P2 receptors Ⅲ fibroblasts Ⅲ atherosclerosis Ⅲ cytokines Ⅲ diabetes Ⅲ apoptosis F ibroblasts are a key structural element of the arterial wall and a target and source of several diffusible factors that regulate the homeostasis of circulating and vessel wall cells. 1,2 They are well known for being the major producers of extracellular matrix, an active source of inflammatory mediators, as well as key players in wound repair and tissue remodeling. 3,4 In human pathology, fibroblast dysfunction is implicated in diseases of unknown etiology, such as scleroderma, but also in chronic degenerative diseases, such as atherosclerosis or diabetic angiopathy. 5,6 In the vessel wall, fibroblasts and smooth muscle cells share several features, and it is well established that within the atherosclerotic plaque, smooth muscle cells may acquire a dedifferentiated phenotype that resembles that of fibroblasts. 7 In turn, activated fibroblasts proliferate and migrate into the plaque, contributing to plaque thickening and fibrous cap formation. 8 In the atheromatous lesion, fibroblasts are the main source of extracellular matrix and the main causative agent of the progressive fibrosis, as well as an active source of mediators that stimulate endothelial cells and promote recruitment of leukocytes, thus accelerating damage of the arterial intima and media. 8 Under certain poorly known conditions, the fibrous cap can undergo thinning and set the conditions for life-threatening plaque rupture. Molecular mechanisms underlying this dramatic outcome are basically unknown, but sudden apoptosis of ...

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“…Data are averages SD of six measurements from three separate experiments the major producers of extracellular matrix but also a cell type actively involved in the synthesis of inflammatory mediators and in tissue repair [34]. Furthermore, they share several characteristics with vascular smooth muscle cells, participating in the regulation of vascular tone [35]. They also participate in the development of the early steps of atherosclerotic damage and have an important role in the pathogenesis of the typical changes in extracellular matrix [36] observed in diabetes.…”

Section: Discussionmentioning

confidence: 99%

High glucose modulates P2X 7 receptor-mediated function in human primary fibroblasts

et al. 2000

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Extracellular ATP triggers a variety of responses in several cell types, including contraction of smooth muscle cells [1], regulation of nitric oxide production from endothelium [2], stimulation of cytokine release from immune cells [3,4], and modulation of several other metabolic pathways [5,6]. Moreover, it is a strong stimulus for insulin release from isolated pancreas and beta cells [7,8], which points to a potentially important role for this nucleotide in the control of blood glucose. Recently, ATP receptors have also been found to be involved in the regulation of GLUT-4 expression in cardiomiocytes [9].The receptors mediating these diverse effects have been described as P2 purinoreceptors and are divided into two subgroups: P2Y and P2X receptors [10]. The P2Y are seven membrane spanning, and G proteincoupled receptors, linked to inositol phosphate and diacylglycerol formation. They are nearly ubiquitous, have a high affinity for ATP (K m in the nano-micro Diabetologia (2000) Results. We show that cells grown in a medium with high glucose concentration underwent great ATPmediated morphological changes, enhanced apoptosis, caspase 3 activation and interleukin-6 release. We identified P2X 7 as the main purinergic receptor involved in these responses. Furthermore, high glucose concentration triggered the assembly of P2X 7 into ring-like structures located at the periphery of the cells. Conclusion/interpretation. Given that ATP is frequently released into the extracellular milieu upon cell and tissue damage, secretory exocytosis or activation of plasma membrane transporters, we hypothesize that ATP receptors participate in the pathogenesis of vascular complications of diabetes.

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Interaction of endothelial cells and fibroblasts with modified fibrin networks: role in atherosclerosis

Cited by 31 publications

References 16 publications

Denser plasma clot formation and impaired fibrinolysis in paroxysmal and persistent atrial fibrillation while on sinus rhythm: Association with thrombin generation, endothelial injury and platelet activation

Denser plasma clot formation and impaired fibrinolysis in paroxysmal and persistent atrial fibrillation while on sinus rhythm: Association with thrombin generation, endothelial injury and platelet activation

Enhanced P2X₇Activity in Human Fibroblasts From Diabetic Patients

High glucose modulates P2X 7 receptor-mediated function in human primary fibroblasts

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Interaction of endothelial cells and fibroblasts with modified fibrin networks: role in atherosclerosis

Cited by 31 publications

References 16 publications

Denser plasma clot formation and impaired fibrinolysis in paroxysmal and persistent atrial fibrillation while on sinus rhythm: Association with thrombin generation, endothelial injury and platelet activation

Denser plasma clot formation and impaired fibrinolysis in paroxysmal and persistent atrial fibrillation while on sinus rhythm: Association with thrombin generation, endothelial injury and platelet activation

Enhanced P2X7Activity in Human Fibroblasts From Diabetic Patients

High glucose modulates P2X 7 receptor-mediated function in human primary fibroblasts

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Resources

About

Enhanced P2X₇Activity in Human Fibroblasts From Diabetic Patients