المؤلفون: Bueno-Betí, Carlos, Novella, Susana, Soleti, Raffaella, Mompeón, Ana, Vergori, Luisa, Sanchís, Juan, Andriantsitohaina, Ramaroson, Martinez, Maria Carmen, Hermenegildo, Carlos

المساهمون: Department of Physiology, University of Valencia, Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)

المصدر: ISSN: 0008-6363 ; Cardiovascular Research ; https://hal.science/hal-03048091Test ; Cardiovascular Research, 2019, 115 (2), pp.409-418. ⟨10.1093/cvr/cvy189⟩.

مصطلحات موضوعية: Acute myocardial infarction, Endothelial progenitor cells, Microparticles, Nitric oxide, Vasculogenesis, [SDV]Life Sciences [q-bio]

الوصف: International audience ; Time for primary review: 28 days Aims Endothelial progenitor cells (EPC) play a role in endothelium integrity maintenance and regeneration. Decreased numbers of EPC or their impaired function correlates with an increase in cardiovascular events. Thus, EPC are important predictors of cardiovascular mortality and morbidity. Microparticles carrying Sonic hedgehog (Shh) morphogen (MP Shhþ) trigger pro-angiogenic responses, both in endothelial cells and in ischaemic rodent models. Here, we propose that MP Shhþ regulates EPC function, thus enhancing vasculogenesis, and correcting the defects in dysfunctional EPC obtained from acute myocardial infarction (AMI) patients.

العلاقة: hal-03048091; https://hal.science/hal-03048091Test; https://hal.science/hal-03048091/documentTest; https://hal.science/hal-03048091/file/CARDIOVASCRES-S-18-00326%20-%20copie.pdfTest

الإتاحة: https://doi.org/10.1093/cvr/cvy189Test
https://hal.science/hal-03048091Test
https://hal.science/hal-03048091/documentTest
https://hal.science/hal-03048091/file/CARDIOVASCRES-S-18-00326%20-%20copie.pdfTest

المؤلفون: Pinaud, Frédéric, Bocquet, Arnaud, Dumont, Odile, Retailleau, Kevin, Baufreton, Christophe, Andriantsitohaina, Ramaroson, Loufrani, Laurent, Henrion, Daniel

المساهمون: Service de chirurgie cardio-vasculaire et thoracique, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Préconditionnement et remodelage du myocarde, Université d'Angers (UA)-UPRES EA 3860, Biologie Neurovasculaire Intégrée (BNVI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INSERM, CNRS, Université d'Angers, Fondation pour la Recherche Médicale (FRM), Fédération Française de Cardiologie (Frederic Pinaud). Conseil Général du Maine et Loire (Arnaud Bocquet), Région des Pays de la Loire (Odile Dumont), contrat d'interface INSERM-CHU d'Angers (D. Henrion).

المصدر: ISSN: 0194-911X.

مصطلحات موضوعية: aging, endothelium, microcirculation, angiotensin II receptors, nitric oxide, oxidative stress, vasodilator agents, MESH: Aging, MESH: Animals, MESH: Rats, Wistar, MESH: Reactive Oxygen Species, MESH: Receptor, Angiotensin, Type 2, MESH: Regional Blood Flow, MESH: Tissue Distribution, MESH: Vascular Resistance, MESH: Vasoconstriction, MESH: Vasodilation, MESH: Vasodilator Agents, MESH: Endothelial Cells, MESH: Hydralazine, MESH: Male, MESH: Mesenteric Arteries, MESH: Muscle, Smooth, Vascular, MESH: Myocytes, Smooth Muscle

الوصف: International audience ; The role of angiotensin II type 2 receptors (AT2Rs) remains a matter of controversy. Its vasodilatory and antitrophic properties are well accepted. Nevertheless, in hypertensive rats, AT2R stimulation induces a vasoconstriction counteracting flow-mediated dilation (FMD). This contraction is reversed by hydralazine. Because FMD is also decreased in aging, another risk factor for cardiovascular diseases, we hypothesized that AT2R function might be altered in old-rat resistance arteries. Mesenteric resistance arteries (250 mum in diameter) were isolated from old (24 months) and control (4 months) rats receiving hydralazine (16 mg/kg per day; 2 weeks) or water. FMD, NO-mediated dilation, and endothelial NO synthase expression were lower in old versus control rats. AT2R blockade improved FMD in old rats, suggesting that AT2R stimulation produced vasoconstriction. AT2R expression was higher in old rats and mainly located in the smooth muscle layer. In old rats, AT2R stimulation induced endothelium-independent contraction, which was suppressed by the antioxidant Tempol. Reactive oxygen species level was higher in old-rat arteries than in controls. Hydralazine improved FMD and NO-dependent dilation in old rats without change in AT2R expression and location. In old rats treated with hydralazine, reactive oxygen species level was reduced in endothelial and smooth muscle cells, and AT2R-dependent contraction was abolished. Thus, AT2R stimulation induced vasoconstriction through activation of reactive oxygen species production, contributing to decrease FMD in old-rat resistance arteries. Hydralazine suppressed AT2R-dependent reactive oxygen species production and AT2R-dependent contraction, improving FMD. Importantly, endothelial alterations in aging were reversible. These findings are important to consider in the choice of vasoactive drugs in aging.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/17485601; inserm-00145263; https://inserm.hal.science/inserm-00145263Test; https://inserm.hal.science/inserm-00145263/documentTest; https://inserm.hal.science/inserm-00145263/file/Pinaud_AT2R07-HAL.pdfTest; PUBMED: 17485601

الإتاحة: https://doi.org/10.1161/HYPERTENSIONAHA.106.085035Test
https://inserm.hal.science/inserm-00145263Test
https://inserm.hal.science/inserm-00145263/documentTest
https://inserm.hal.science/inserm-00145263/file/Pinaud_AT2R07-HAL.pdfTest

المؤلفون: Recoquillon, Sylvain, Carusio, Nunzia, Lagrue Lakhal, Anne Hélène, Tual Chalot, Simon, FILIPPELLI, Amelia, Andriantsitohaina, Ramaroson, Martinez, M. Carmen

المساهمون: Recoquillon, Sylvain, Carusio, Nunzia, Lagrue Lakhal, Anne Hélène, Tual Chalot, Simon, Filippelli, Amelia, Andriantsitohaina, Ramaroson, Martinez, M. Carmen

مصطلحات موضوعية: NF-κB, inflammation, lipopolysaccharide, nitric oxide, nmMLCK, Animal, Aorta, Cells, Cultured, Endothelium, Vascular, Human, In Vitro Technique, Male, Mice, Knockout, Myosin-Light-Chain Kinase, NF-kappa B, Nitric Oxide Synthase Type II, Sepsis

الوصف: During sepsis, endothelial barrier dysfunction contributes to cardiovascular failure, mainly through the release of oxidative metabolites by penetrant leukocytes. We reported the non-muscular isoform of myosin light chain kinase (nmMLCK) playing a pivotal role in endotoxin shock injury associated with oxidative and nitrative stresses, and vascular hyporeactivity. The present study was aimed at understanding the molecular mechanism of lipopolysaccharide (LPS)-induced vascular alterations as well as studying a probable functional association of nmMLCK with nuclear factor κ-light-chain enhancer of activated B cells (NF-κB). Aortic rings from mice were exposed invitro to LPS and, then, vascular reactivity was measured. Human aortic endothelial cells (HAoECs) were incubated with LPS, and interaction of nmMLCK with NF-κB was analysed. We provide evidence that nmMLCK deletion prevents vascular hyporeactivity induced by invitro LPS treatment but not endothelial dysfunction in the aorta. Deletion of nmMLCK inhibits LPS-induced NF-κB activation and increases nitric oxide (NO) release via induction of inducible NO synthase (iNOS) within the vascular wall. Also, removal of endothelium prevented both NF-κB and iNOS expression in aortic rings. Among the proinflammatory factors released by LPS-treated endothelial cells, interleukin-6 accounts for the induction of iNOS on smooth muscle cells in response to LPS. Of particular interest is the demonstration that, in HAoECs, LPS-induced NF-κB activation occurs via increased MLCK activity sensitive to the MLCK inhibitor, ML-7, and physical interactions between nmMLCK and NF-κB. We report for the first time on NF-κB as a novel partner of nmMLCK within endothelial cells. The present study demonstrates a pivotal role of nmMLCK in vascular inflammatory pathologies.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/26201020; info:eu-repo/semantics/altIdentifier/wos/WOS:000361047000002; volume:129; firstpage:687; lastpage:698; numberofpages:12; journal:CLINICAL SCIENCE; http://hdl.handle.net/11386/4653346Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84942909095; http://www.clinsci.org/content/129/8/687.longTest

الإتاحة: https://doi.org/10.1042/CS20140625Test
http://hdl.handle.net/11386/4653346Test
http://www.clinsci.org/content/129/8/687.longTest

المؤلفون: Boisramé-Helms, Julie, Meziani, Ferhat, Sananès, Nicolas, Boisramé, Thomas, Langer, Bruno, Schneider, Francis, Ragot, Thierry, Andriantsitohaina, Ramaroson, Tesse, Angela

المساهمون: Service de Réanimation Médicale Strasbourg, Les Hôpitaux Universitaires de Strasbourg (HUS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Service de gynécologie–obstétrique, Centre Hospitalier Universitaire Strasbourg (CHU Strasbourg), Les Hôpitaux Universitaires de Strasbourg (HUS)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Hôpital de Hautepierre Strasbourg, Hôpital de Hautepierre Strasbourg, Vectorologie et thérapeutiques anti-cancéreuses Villejuif (UMR 8203), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), ITX - unité de recherche de l'institut du thorax (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)

المصدر: ISSN: 0767-3981.

مصطلحات موضوعية: Female, Signal Transduction, Pregnancy, Young Adult, Cell-Derived Microparticles, Nitric Oxide, Cyclooxygenase 2, Nitric Oxide Synthase Type II, Dose-Response Relationship, Drug, NF-kappa B, Hypertension, Inflammation Mediators, Arteries, Vasoconstriction, Vasoconstrictor Agents, Pre-Eclampsia, Cyclooxygenase 2 Inhibitors, Omentum, preeclampsia, Tissue Culture Techniques, vascular inflammation, humans, adult, Oxidative stress, [SDV]Life Sciences [q-bio]

الوصف: International audience ; Elevated plasmatic levels of lympho-monocyte and platelet microparticles (MPs) have been reported in preeclampsia. Previous studies suggest that MPs could participate in preeclampsia vascular impairment. In this study, we investigated the ex vivo vascular effects of MPs from preeclamptic women on arteries from normotensive pregnant women. Omental arteries were collected from normal pregnant women undergoing cesarean section and incubated during 24 h with MPs from normal pregnant or preeclamptic women. Vascular contraction to serotonin and phenylephrine was studied on a wire myograph with or without pharmacological selective inhibitors of inducible nitric oxide synthase (iNOS) and/or cyclo-oxygenase-2 (COX-2). Expression of iNOS, COX-2, and NF-κB and production of superoxide anion and 8-isoprostane were also assessed by immunohistological or biochemical staining and/or Western blot or ELISA assay, respectively. Microparticles from preeclamptic women, but not those from normal pregnant women, induced hyporeactivity to vasocontracturant agonists in omental arteries. Selective inhibitor of iNOS partially restored this arterial contraction, suggesting that nitric oxide (NO) is involved in vascular contractility alteration. Conversely, COX-2 induced 8-isoprostane release, a vasoconstricting metabolite modulating the agonist-induced contraction. COX-2 selective inhibitor almost abolished the arterial contraction in the same vessels. Interestingly, the association of iNOS and COX-2 selective inhibitors restored the contraction to control levels. Moreover, iNOS, COX-2, and NF-κB expressions are upregulated and superoxide anion levels increased in vessels incubated with MPs from preeclamptic women. In conclusion, circulating MPs from preeclamptic women induce vascular inflammation and enhance oxidative stress. These results suggest a possible role of MPs during preeclampsia-induced arterial dysfunction.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/26213341; hal-01830586; https://hal.science/hal-01830586Test; PUBMED: 26213341

الإتاحة: https://doi.org/10.1111/fcp.12136Test
https://hal.science/hal-01830586Test

المؤلفون: Benarbia, Mohammed El Amine, Macherel, David, Faure, Sébastien, Jacques, Caroline, Andriantsitohaina, Ramaroson, Malthièry, Yves

المساهمون: Institut de Recherche en Horticulture et Semences (IRHS), Université d'Angers (UA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-INSTITUT AGRO Agrocampus Ouest, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)

المصدر: ISSN: 0041-008X.

مصطلحات موضوعية: Organochlorine, Mitochondria, Nitric oxide, Energetic metabolism, OXPHOS, [SDV.TOX]Life Sciences [q-bio]/Toxicology

الوصف: International audience ; Lindane (LD) is a persistent environmental pollutant that has been the subject of several toxicological studies. However, concentrations used in most of the reported studies were relatively higher than those found in the blood of the contaminated area residents and effects of low concentrations remain poorly investigated. Moreover, effects on cell metabolism and mitochondrial function of exposure to LD have received little attention. This study was designed to explore the effects of low concentrations of LD on cellular metabolism and mitochondrial function, using the hepatocarcinoma cell line HepG2.Cells were exposed to LD for 24, 48 and 72 h and different parameters linked with mitochondrial regulation and energy metabolism were analyzed.Despite having any impact on cellular viability, exposure to LD at plasmatic concentrations led to an increase of maximal respiratory capacity, complex I activity, intracellular ATP and NO release but decreased uncoupled respiration to ATP synthesis and medium lactate levels. In addition, LD exposure resulted in the upregulation of mitochondrial biogenesis genes.We suggest that, at plasmatic concentrations, LD acts as a metabolic disruptor through impaired mitochondrial function and regulation with an impact on cellular energetic metabolism. In addition, we propose that a cellular assay based on the analysis of mitochondria function, such as described here for LD, may be applicable for larger studies on the effects of low concentrations of xenobiotics, because of the exquisite sensitivity of this organelle.

العلاقة: hal-03218067; https://univ-angers.hal.science/hal-03218067Test

الإتاحة: https://doi.org/10.1016/j.taap.2013.06.006Test
https://univ-angers.hal.science/hal-03218067Test

المؤلفون: Lavaud, Alexis, Soletia, Raffaella, Hay, Anne-Emmanuelle, Richomme, Pascal, Guilet, David, Andriantsitohaina, Ramaroson

المساهمون: Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Substances d'Origine Naturelle et Analogues Structuraux (SONAS), Université d'Angers (UA), Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

المصدر: ISSN: 0006-2952.

مصطلحات موضوعية: Endothelium, Angiogenesis, Clusiaceae, Xanthone, Nitric oxide, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology

الوصف: International audience ; Clusiaceae plants display high contents of xanthones and coumarins, the effects of which on endothelium, more particularly on angiogenesis, have not been assessed yet. We screened the capacity of six molecules from Clusiaceae - belonging to xanthones, coumarins and acid chromanes classes - to induce endothelium-dependent relaxation on mice aortic rings. Endothelial nitric oxide (NO) production was assessed in endothelial cell line using electron paramagnetic resonance technique. Then, the capacity of these molecules to induce capillary-like structures of endothelial cells was assessed. Cellular processes implicated in angiogenesis (adhesion, migration and proliferation) and Western blot analyses were then investigated. Among the tested molecules, isocalolongic acid (IA) and 2-deprenylrheediaxanthone (DRX) induced an endothelium-dependent relaxation of the aorta associated with an increase of NO production in endothelial cells. Using in vitro and ex vivo angiogenesis assays, it was shown that IA treatment promoted the formation of capillary-like network. In contrast, DRX prevented the ability of vascular endothelial growth factor (VEGF) to increase the formation of capillary-like network. IA increased endothelial cell proliferation while DRX decreased all cellular processes of angiogenesis. Western blot analysis showed that IA increased VEGF expression whereas DRX decreased ICAM-1 expression. Altogether, these data allowed identifying isolated molecules from Clusiaceae that exhibit a potential activity towards the modulation of endothelium-dependent relaxation involving NO release. Interestingly, they also highlighted paradoxical effects of the two compounds on cellular angiogenic processes, IA being pro-angiogenic and DRX anti-angiogenic.

العلاقة: halsde-00722703; https://hal.science/halsde-00722703Test; PRODINRA: 244774; WOS: 000299452200010

الإتاحة: https://doi.org/10.1016/j.bcp.2011.12.002Test
https://hal.science/halsde-00722703Test

المؤلفون: Tual-Chalot, Simon, Fatoumata, Keita, Priou, Pascaline, Trzepizur, Wojciech, Gaceb, Abderahim, Contreras, Cristina, Prieto, Dolores, Martinez, Maria Carmen, Gagnadoux, Frédéric, Andriantsitohaina, Ramaroson

المساهمون: Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)

المصدر: ISSN: 1525-2191 ; The American journal of pathology ; https://univ-angers.hal.science/hal-03275872Test ; The American journal of pathology, 2012, 181 (4), pp.1473 - 1482. ⟨10.1016/j.ajpath.2012.06.020⟩.

مصطلحات موضوعية: Adult, Aged, Animals, Aorta, Cell-Derived Microparticles, Cyclooxygenase 2, Down-Regulation, Endothelium, Vascular, Humans, Male, Mice, Middle Aged, Nitric oxide, Nitric Oxide Synthase Type III, Phenotype, Serotonin, Signal Transduction, Sleep Apnea, Obstructive, Superoxide Dismutase, vasoconstriction, Vasoconstrictor Agents, Young Adult, [SDV]Life Sciences [q-bio]

الوصف: International audience ; Obstructive sleep apnea (OSA) is characterized by repetitive apnea-hypopnea cycles during sleep associated with oxygen desaturation and sleep disruption. We evaluated the role of circulating microparticles (MPs) from patients with OSA in the regulation of vascular function. MPs from whole blood from patients with OSA or control subjects were injected i.v. into mice. Injection of MPs from patients with OSA induced ex vivo vascular hyperreactivity in aortas with functional endothelium but, in contrast, hyporeactivity in vessels without functional endothelium. Vascular hyperreactivity was blunted in the presence of a nitric oxide synthase inhibitor alone or combined with the cyclooxygenase inhibitor indomethacin. MPs from patients with OSA reduced endothelial nitric oxide synthase activity and nitric oxide production, increased aortic cyclooxygenase-1 and cyclooxygenase-2 expression, and increased thromboxane A(2) and prostacyclin production. Blockade of thromboxane A(2) receptor did not affect the serotonin response in arteries from OSA MP-treated mice. A superoxide dismutase mimetic reduced the vascular hyperreactivity induced by MPs from patients with OSA but had no effect on contraction in vessels from control and non-OSA MP-treated mice. These data provide evidence that circulating MPs from patients with OSA induce ex vivo vascular hyperreactivity with the obligatory role of the endothelium and subtle interactions between the nitric oxide and cyclooxygenase pathways and metabolites. These results highlight the participation of MPs in vascular dysfunction associated with OSA.

العلاقة: hal-03275872; https://univ-angers.hal.science/hal-03275872Test; OKINA: ua372

الإتاحة: https://doi.org/10.1016/j.ajpath.2012.06.020Test
https://univ-angers.hal.science/hal-03275872Test

المؤلفون: Soleti, Raffaella, Lauret, Emilie, Andriantsitohaina, Ramaroson, Martínez, M. Carmen

المساهمون: Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)

المصدر: ISSN: 1873-4596 ; Free radical biology & medicine ; https://univ-angers.hal.science/hal-03328684Test ; Free radical biology & medicine, 2012, 53, pp.2159-2170. ⟨10.1016/j.freeradbiomed.2012.09.021⟩.

مصطلحات موضوعية: Antioxidants, Apoptosis, Caspases, Catalase, Cell Line, Cell-Derived Microparticles, Dactinomycin, Enzyme Induction, Hedgehog Proteins, Human Umbilical Vein Endothelial Cells, Humans, Nitric oxide, Oxidative Stress, Reactive Oxygen Species, Signal Transduction, Superoxide Dismutase, [SDV]Life Sciences [q-bio]

الوصف: International audience ; Microvesicles are plasma membrane-derived fragments released from various cell types during activation and/or apoptosis and posses the ability to deliver biological information between cells. Microvesicles generated from T lymphocytes undergoing activation and apoptosis bear the morphogen Sonic Hedgehog, and exert a beneficial potential effect on the cardiovascular system through their dual capacity to increase nitric oxide and reduce reactive oxygen species production. This study investigated the effect of microvesicles on the apoptosis of human umbilical vein endothelial cells triggered by actinomycin D. Microvesicles prevented apoptosis induced by actinomycin D by modulating reactive oxygen species production: during the early phase of apoptosis, microvesicles might act directly as reactive oxygen species scavengers, owing to their ability to carry active antioxidant enzymes, catalase, and isoforms of the superoxide dismutase. Furthermore, their effects were associated with the ability to increase the expression of manganese-superoxide dismutase in endothelial cells, through the internalization process. Interestingly, microvesicles bearing Sonic Hedgehog induced cytoprotection in endothelial cells through the activation of the Sonic Hedgehog pathway. These findings provide additional evidence that microvesicles from T lymphocytes exert their vasculoprotective effects by promoting internalization and induction of antioxidant messages to the endothelial monolayer.

العلاقة: hal-03328684; https://univ-angers.hal.science/hal-03328684Test; OKINA: ua6729

الإتاحة: https://doi.org/10.1016/j.freeradbiomed.2012.09.021Test
https://univ-angers.hal.science/hal-03328684Test

المؤلفون: Mastronardi, Maria, Mostefai, Hadj, Soleti, Raffaella, Agouni, Abdelali, Martinez, Maria Carmen, Andriantsitohaina, Ramaroson

المساهمون: Mitochondrie : Régulations et Pathologie, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie Neurovasculaire Intégrée (BNVI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université d'Angers (UA), Stress Oxydant et Pathologies Métaboliques (SOPAM)

المصدر: ISSN: 0767-3981.

مصطلحات موضوعية: Apoptosis, Caveolin 1, Cell Line, Cell-Derived Microparticles, Endothelial Cells, Gene Expression Regulation, Humans, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Monocytes, Nitric oxide, Oxidative Stress, Phosphatidylinositol 3-Kinases, Signal Transduction, [SDV]Life Sciences [q-bio]

الوصف: International audience ; Microparticles are membrane vesicles with procoagulant and proinflammatory properties released during cell activation or apoptosis. Microparticles from monocytes have been implicated in atherosclerosis and vascular inflammation, but their direct effects on endothelial cells are not completely elucidated. The present study was designed to dissect the signaling pathways of monocytic microparticles in endothelial cells with respect to both NO pathway and reactive oxygen species. Microparticles were produced by treatment of human monocytic cell line THP-1 with the apoptotic agent VP-16. Human endothelial cells were treated with monocytic microparticles and then, we studied their effects on nitrosative and oxidative stresses. Incubation of human endothelial cells with microparticles enhanced the production of NO without affecting superoxide anions generation. Microparticles did not affect endothelial NO synthase expression and its phosphorylation. Interestingly, microparticles decreased caveolin-1 expression and increased its phosphorylation. Inhibition of PI-3-kinase or MEK1/2 reversed the effects of microparticles on caveolin-1 expression but not its phosphorylation. Moreover, microparticles increased nitration of several proteins, reflecting peroxynitrite production, which was prevented by blockade of PI-3-kinase pathway. In summary, monocyte microparticles active multiple pathways related to nitrosative stress in endothelial cells including both PI-3-kinase and ERK1/2 in the regulation of caveolin-1 expression. These data underscore the pleiotropic effect of microparticles on endothelial cells and suggest that they probably play a critical role on vascular function.

العلاقة: hal-03276657; https://univ-angers.hal.science/hal-03276657Test; OKINA: ua10803

الإتاحة: https://doi.org/10.1111/j.1472-8206.2010.00898.xTest
https://univ-angers.hal.science/hal-03276657Test

المؤلفون: Priou, Pascaline, Gagnadoux, Frédéric, Tesse, Angela, Mastronardi, Maria, Agouni, Abdelali, Meslier, Nicole, Racineux, Jean-Louis, Martinez, Maria Carmen, Trzepizur, Wojciech, Andriantsitohaina, Ramaroson

المساهمون: Mitochondrie : Régulations et Pathologie, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA), Biologie Neurovasculaire Intégrée (BNVI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de pneumologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Stress Oxydant et Pathologies Métaboliques (SOPAM)

المصدر: ISSN: 1525-2191 ; The American journal of pathology ; https://univ-angers.hal.science/hal-03275675Test ; The American journal of pathology, 2010, 177 (2), pp.974 - 983. ⟨10.2353/ajpath.2010.091252⟩.

مصطلحات موضوعية: Adolescent, Adult, Aged, Angiogenesis Inducing Agents, Animals, Cell Adhesion Molecules, Cell-Derived Microparticles, Electron Spin Resonance Spectroscopy, Endothelial Cells, Endothelium, Vascular, Humans, Male, Mice, Middle Aged, Nitric oxide, Reactive Oxygen Species, RNA, Messenger, Sleep Apnea, Obstructive, Young Adult, [SDV]Life Sciences [q-bio]

الوصف: International audience ; Endothelial dysfunction is involved in vascular complications of obstructive sleep apnea (OSA). In this study, circulating microparticles (MPs) from patients with OSA-induced nocturnal desaturations were characterized and their effects on endothelial function were evaluated. Two age-matched groups of patients undergoing polysomnography for OSA were compared: 35 desaturators with a 3% oxyhemoglobin desaturation index (ODI) > or = 10 events per hour of sleep and 27 nondesaturators with ODI <10 events per hour. MPs were characterized by flow cytometry and then either used to treat in vitro human endothelial cells or to study endothelial function in mice. Circulating MPs did not differ between groups, but MPs from granulocytes and activated leukocytes (CD62L(+)) were found at higher levels in desaturators. In vitro, MPs from desaturators reduced endothelial nitric oxide (NO) production by enhancing phosphorylation of endothelial NO synthase at the site of inhibition and expression of caveolin-1. CD62L(+) MPs positively correlated with ODI. Endothelial NO production negatively correlated with both CD62L(+) MPs and ODI. MPs from desaturators increased expression of endothelial adhesion molecules including E-selectin, ICAM-1 and ITGA5, and cyclooxygenase 2. Moreover, injection of MPs from desaturators into mice impaired endothelium-dependent relaxation in aorta and flow-induced dilation in small mesenteric arteries. This study demonstrates an association between endothelial dysfunction and increased circulating levels of CD62L(+) MPs. This may initiate atherogenic processes in patients with OSA and severe nighttime hypoxia.

العلاقة: hal-03275675; https://univ-angers.hal.science/hal-03275675Test; OKINA: ua340; PUBMEDCENTRAL: PMC2913357

الإتاحة: https://doi.org/10.2353/ajpath.2010.091252Test
https://univ-angers.hal.science/hal-03275675Test