Markers of Endothelial Dysfunction

Müller, Mathias M.; Griesmacher, Andrea

doi:10.1515/cclm.2000.013

Cited by 51 publications

(31 citation statements)

References 34 publications

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“…2,[4][5][6][7][8] The molecules that comprise the ROS family are oxidative molecules including the superoxide radical (O 2 Á À ), hydrogen peroxide (H 2 O 2 ), and the hydroxyl radical ( Á OH), among several others. 1,2 During systemic inflammation, ROS circulate in the bloodstream and can interact directly with endothelial cells (ECs) in the inner wall of blood vessels, 1,9 which increases intracellular oxidative stress in ECs. Therefore, the ROS are generated within the endothelial monolayer and raise the intracellular level of oxidative stress in ECs.…”

mentioning

confidence: 99%

Oxidative stress mediates the conversion of endothelial cells into myofibroblasts via a TGF-β1 and TGF-β2-dependent pathway

Montorfano

Becerra

Cerro

et al. 2014

Laboratory Investigation

120

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During the pathogenesis of systemic inflammation, reactive oxygen species (ROS) circulate in the bloodstream and interact with endothelial cells (ECs), increasing intracellular oxidative stress. Although endothelial dysfunction is crucial in the pathogenesis of systemic inflammation, little is known about the effects of oxidative stress on endothelial dysfunction. Oxidative stress induces several functions, including cellular transformation. A singular process of cell conversion is tendothelial-to-mesenchymal transition, in which ECs become myofibroblasts, thus losing their endothelial properties and gaining fibrotic behavior. However, the participation of oxidative stress as an inductor of conversion of ECs into myofibroblasts is not known. Thus, we studied the role played by oxidative stress in this conversion and investigated the underlying mechanism. Our results show that oxidative stress induces conversion of ECs into myofibroblasts through decreasing the levels of endothelial markers and increasing those of fibrotic and ECM proteins. The underlying mechanism depends on the ALK5/Smad3/NF-kB pathway. Oxidative stress induces the expression and secretion of TGF-b1 and TGF-b2 and p38 MAPK phosphorylation. Downregulation of TGF-b1 and TGF-b2 by siRNA technology abolished the H 2 O 2 -induced conversion. To our knowledge, this is the first report showing that oxidative stress is able to induce conversion of ECs into myofibroblasts via TGF-b secretion, emerging as a source for oxidative stress-based vascular dysfunction. Thus, oxidative stress emerges as a decisive factor in inducing conversion of ECs into myofibroblasts through a TGF-b-dependent mechanism, changing the ECs protein expression profile, and converting normal ECs into pathological ones. This information will be useful in designing new and improved therapeutic strategies against oxidative stress-mediated systemic inflammatory diseases.

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confidence: 99%

Oxidative stress mediates the conversion of endothelial cells into myofibroblasts via a TGF-β1 and TGF-β2-dependent pathway

Montorfano

Becerra

Cerro

et al. 2014

Laboratory Investigation

120

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“…IR may be linked to endothelial dysfunction by a number of molecular and pathophysiological mechanisms, such as disturbances of subcellular signaling pathways and the PI-3-kinase/Akt pathway, common to both insulin action and nitric oxide production [16]. In the present study we amplified and defined this finding, showing that the metformin-induced improvement of EFR was closely linked with HOMA-IR baseline values: an increase of EFR was observed only in patients with higher levels of HOMA-IR.…”

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confidence: 99%

Cardiopulmonary and endothelial effects of metformin treatment in an insulin resistant population

Cadeddu

Deidda

Cadeddu

et al. 2012

International Journal of Cardiology

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“…MBL is capable of binding to certain phospholipids, oligosaccharide structures and glycosylated IgG [16, 17, 18], and may thus participate in the clearance of antigen-antibody complexes from the circulation. Thus the number of these immune complexes may be increased in persons with MBL deficiency, this possibly causing endothelial damage and contributing to hypercoagulability and thrombocyte aggregation/activation via ligation of FcγRII receptors as well as intimal hyperplasia [19, 20]. Furthermore, it should be noted that MBL is an acute-phase reactant, and several genetic variants with significantly varying physicochemical characteristics of the MBL molecule exist which cause functional MBL deficiency [4, 21].…”

Section: Discussionmentioning

confidence: 99%

Association of Mannan-Binding Lectin Deficiency with Venous Bypass Graft Occlusions in Patients with Coronary Heart Disease

Limnell¹,

Aittoniemi

Vaarala

et al. 2002

Cardiology

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We investigated the effect of mannan-binding lectin (MBL) deficiency on the susceptibility to bypass graft occlusion in 62 patients with coronary heart disease. MBL deficiency appeared to be associated with occlusion (p = 0.0099). A high level of anti-cardiolipin IgG as well as the number of venous bypass grafts were also involved (p = 0.0018 and p = 0.0104, respectively). Since early occlusion (<5 years after surgery) of a venous bypass graft is considered to be caused by thrombosis or fibro-intimal hyperplasia superimposed by thrombosis, our finding also implies an association of MBL deficiency with thrombotic events. It remains unclear whether the previously confirmed effect of MBL deficiency in coronary disease is mediated through this possible thrombotic mechanism, or whether plaque formation is also involved in the process. Further studies are clearly warranted.

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Markers of Endothelial Dysfunction

Cited by 51 publications

References 34 publications

Oxidative stress mediates the conversion of endothelial cells into myofibroblasts via a TGF-β1 and TGF-β2-dependent pathway

Oxidative stress mediates the conversion of endothelial cells into myofibroblasts via a TGF-β1 and TGF-β2-dependent pathway

Cardiopulmonary and endothelial effects of metformin treatment in an insulin resistant population

Association of Mannan-Binding Lectin Deficiency with Venous Bypass Graft Occlusions in Patients with Coronary Heart Disease

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