Sonic hedgehog carried by microparticles corrects endothelial injury through nitric oxide release

Agouni, Abdelali; Mostefai, Hadj Ahmed; Porro, Chiara; Carusio, Nunzia; Favre, Julie; Richard, Vincent; Henrion, Didier; Martínez, María Carmen; Andriantsitohaina, Ramaroson

doi:10.1096/fj.07-8079com

Cited by 149 publications

(145 citation statements)

References 31 publications

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“…21 Cells were treated for 24 hours by MPs from patients or healthy subjects at the circulating levels of MPs detected in the blood of each patient or healthy subject, as previously performed in other pathologies. 22,23 In another set of experiments, cells were treated with vehicle (anti-CD61 microbeads alone), platelet-or nonplatelet-derived MPs from MS patients before NO production being assessed.…”

Section: Cell Culturementioning

confidence: 99%

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Endothelial Dysfunction Caused by Circulating Microparticles from Patients with Metabolic Syndrome

Agouni

Lagrue-Lak-Hal

Ducluzeau

et al. 2008

The American Journal of Pathology

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246

207

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Microparticles are membrane vesicles that are released during cell activation and apoptosis. Elevated levels of microparticles occur in many cardiovascular diseases; therefore, we characterized circulating microparticles from both metabolic syndrome (MS) patients and healthy patients. We evaluated microparticle effects on endothelial function; however, links between circulating microparticles and endothelial dysfunction have not yet been demonstrated. Circulating microparticles and their cellular origins were examined by flow cytometry of blood samples from patients and healthy subjects. Microparticles were used either to treat human endothelial cells in vitro or to assess endothelium function in mice after intravenous injection. MS patients had increased circulating levels of microparticles compared with healthy patients, including microparticles from platelet, endothelial, erythrocyte, and procoagulant origins. In vitro treatment of endothelial cells with microparticles from MS patients reduced both nitric oxide (NO) and superoxide anion production, resulting in protein tyrosine nitration. These effects were associated with enhanced phosphorylation of endothelial NO synthase at the site of inhibition. The reduction of O 2 ؊ was linked to both reduced expression of p47 phox of NADPH oxidase and overexpression of extracellular superoxide dismutase. The decrease in NO production was triggered by nonplatelet-derived microparticles. In vivo injection of MS microparticles into mice impaired endothelium-dependent relaxation and decreased endothelial NO synthase expression. These data provide evidence that circulating microparticles from MS patients influence endothelial dysfunction. (Am J Pathol

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Section: Cell Culturementioning

confidence: 99%

“…21,24 Briefly, cells were treated with 250 l of colloid Fe(DETC) 2 and incubated at 37°C for 45 minutes. NO measurement was performed on a tabletop x-band spectrometer miniscope (MS200; Magnettech, Berlin, Germany).…”

Section: No Spin Trapping and Electronic Paramagnetic Resonance (Epr)mentioning

confidence: 99%

Endothelial Dysfunction Caused by Circulating Microparticles from Patients with Metabolic Syndrome

Agouni

Lagrue-Lak-Hal

Ducluzeau

et al. 2008

The American Journal of Pathology

Self Cite

246

207

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“…injection into the tail vein of MPs (10 g/ml) as previously described (13). After 24 h, aortic rings were isolated and mounted on a wire myograph.…”

Section: Vascular Reactivitymentioning

confidence: 99%

“…Besides, the above effects of MPs are related to their components, which depend on cell origin and on stimuli used to generate them (11,12). Thus, in previous studies, we have shown that MPs generated from activated/apoptotic lymphocytes induced cell differentiation and NO production by a morphogen-dependent mechanism (12,13). In contrast, when MPs were produced from apoptotic lymphocytes, they did not bear morphogen, resulting in a lack of cell differentiation (12) and they induced vascular dysfunction (8,14).…”

mentioning

confidence: 95%

Phosphatidylinositol 3-Kinase and Xanthine Oxidase Regulate Nitric Oxide and Reactive Oxygen Species Productions by Apoptotic Lymphocyte Microparticles in Endothelial Cells

Mostefai

Agouni

Carusio

et al. 2008

The Journal of Immunology

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Microparticles (MPs) are membrane vesicles released during cell activation and apoptosis. We have previously shown that MPs from apoptotic T cells induce endothelial dysfunction, but the mechanisms implicated are not completely elucidated. In this study, we dissect the pathways involved in endothelial cells with respect to both NO and reactive oxygen species (ROS). Incubation of endothelial cells with MPs decreased NO production that was associated with overexpression and phosphorylation of endothelial NO synthase (eNOS). Also, MPs enhanced expression of caveolin-1 and decreased its phosphorylation. Microparticles enhanced ROS by a mechanism sensitive to xanthine oxidase and P-IκBα inhibitors. PI3K inhibition reduced the effects of MPs on eNOS, but not on caveolin-1, whereas it enhanced the effects of MPs on ROS production. Microparticles stimulated ERK1/2 phosphorylation via a PI3K-depedent mechanism. Inhibition of MEK reversed eNOS phosphorylation but had no effect on ROS production induced by MPs. In vivo injection of MPs in mice impaired endothelial function. In summary, MPs activate pathways related to NO and ROS productions through PI3K, xanthine oxidase, and NF-κB pathways. These data underscore the pleiotropic effects of MPs on NO and ROS, leading to an increase oxidative stress that may account for the deleterious effects of MPs on endothelial function.

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“…For example, anti-coagulant endothelial derived microparticles bearing protein C receptor (54,55) and urokinase-type plasminogen activator (56) have recently been described, whilst T cell MP that can enhance NO-mediated vasorelaxation have also been identified (57). Further work is required to determine whether there is a sub-population of microparticles elicited during the blood:vascular cell interactions described here that function as a negative feedback mechanism to counteract detrimental pro-atherogenic signaling pathways, whether induced by microparticles or other circulating factors.…”

Section: Original Articlementioning

confidence: 99%

Microparticle formation after co‐culture of human whole blood and umbilical artery in a novel in vitro model of flow

2011

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Cardiovascular disease (CVD) is now the largest killer in western society, and the importance of interactions between vascular endothelium and circulating blood components in disease pathogenesis is well established. Microparticles are a heterogeneous population of \1 lm blood borne particles that arise from blebbing or shedding of cell membranes. The microparticle population includes several classes of apoptotic bodies; however, increased numbers of procoagulant microparticles have been described in plasma from people with CVD. We have previously demonstrated that interactions of monocytes and platelets with isolated inflamed endothelial cells lead to production of pro-coagulant tissue factor bearing microparticles under laminar flow conditions. Here we have investigated microparticle production after perfusion of human whole blood through intact inflamed human umbilical artery. When blood was perfused through umbilical arteries which had been pre-stimulated with tumour necrosis factor (TNFa) for 18 h under flow conditions, there was significantly increased production of microparticles from both platelet and non-platelet sources, in particular from erythrocytes. To determine whether microparticles generated during interactions with inflamed endothelium could induce a pro-inflammatory response in trans, we isolated microparticles by centrifugation after co-culture and incubated with isolated quiescent endothelial cells followed by measurement of reactive oxygen species formation. Microparticles derived from co-culture with inflamed endothelium induced significantly enhanced levels of reactive oxygen species (ROS). These data suggest that presence of an inflamed endothelium causes release of pro-inflammatory microparticles from circulating blood cells, which could contribute to prolonged endothelial activation and subsequent atherosclerotic changes in blood vessels subjected to inflammatory insult. ' 2011 International Society for Advancement of Cytometry

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Sonic hedgehog carried by microparticles corrects endothelial injury through nitric oxide release

Cited by 149 publications

References 31 publications

Endothelial Dysfunction Caused by Circulating Microparticles from Patients with Metabolic Syndrome

Endothelial Dysfunction Caused by Circulating Microparticles from Patients with Metabolic Syndrome

Phosphatidylinositol 3-Kinase and Xanthine Oxidase Regulate Nitric Oxide and Reactive Oxygen Species Productions by Apoptotic Lymphocyte Microparticles in Endothelial Cells

Microparticle formation after co‐culture of human whole blood and umbilical artery in a novel in vitro model of flow

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