Critical role of Rap1 in triggering the effects of microparticles from metabolic syndrome patients on vascular smooth muscle cell functions
| العنوان: | Critical role of Rap1 in triggering the effects of microparticles from metabolic syndrome patients on vascular smooth muscle cell functions |
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| المؤلفون: | Raffaella Soleti, M. Laudette, Luisa Vergori, Frédéric Gagnadoux, Frank Lezoualc'h, Samir Henni, Jérôme Boursier, Maggy Chwastyniak, Maria Carmen Martinez, L. Perdomo, X. Vidal-Gomez, Florence Pinet, Ramaroson Andriantsitohaina, Séverine Dubois, Lucie Duluc |
| المساهمون: | Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Martinez, M. Carmen, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC) |
| المصدر: | International Society of Extracellular Vesicles International Society of Extracellular Vesicles, May 2018, Barcelona, Spain HAL |
| بيانات النشر: | HAL CCSD, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | MAPK/ERK pathway, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Vascular smooth muscle, p38 mitogen-activated protein kinases, [SDV]Life Sciences [q-bio], Inflammation, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, 030212 general & internal medicine, Endothelial dysfunction, skin and connective tissue diseases, ComputingMilieux_MISCELLANEOUS, business.industry, nutritional and metabolic diseases, medicine.disease, [SDV] Life Sciences [q-bio], Endocrinology, Rap1, medicine.symptom, Metabolic syndrome, Cardiology and Cardiovascular Medicine, business, Dyslipidemia |
| الوصف: | Introduction The metabolic syndrome (MetS) is a cluster of interrelated risk factors for cardiovascular disease and atherosclerosis including hyperglycemia, dyslipidemia, hypertension and obesity. We have previously shown that circulating levels of microparticles (MPs), small vesicles released from plasma membrane, from MetS patients induce endothelial dysfunction. Objective Here, we analyze whether MPs from MetS patients may participate to the alteration of smooth muscle cells (SMC) function described during the atherosclerosis development. Methods Circulating MPs of non-MetS subjects and MetS patients have been isolated from plasma and characterized by proteomic analysis. Then, the involvement of Rap1 in the effects of MPs on human aortic SMC (HASMC) proliferation and migration was analyzed. Results Differential proteomic analysis of MPs from both types of individuals identifies Rap1, a small GTPase, as two-fold overexpressed in MPs from MetS compared with non-MetS subjects. In addition, Rap1 is in active state, that is, GTP-associated, in both type of MPs. When HASMC are incubated with MPs for 24 h, both types of MPs significantly promote proliferation and migration. Even more, MetS MPs are able to increase the expression of the pro-inflammatory molecules MCP-1 and IL-6. Neutralization of Rap-1 by specific antibody or pharmacological inhibition of Rap-1 with GGTI-298 either partially or completely prevents the effects of MPs from MetS patients but not those from non-MetS MPs. These effects includes HASMC proliferation, migration, inflammation and increase of p38 and ERK5 phosphorylation. Conclusion These data suggest that overexpression of Rap1 in MetS MPs might participate in the enhanced SMC proliferation, migration and activation of MAPK/ERK pathway leading to atherosclerosis. |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9b612bf0490ef29d3d29c9c2a5c8f2d5Test https://hal.archives-ouvertes.fr/hal-02381101Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9b612bf0490ef29d3d29c9c2a5c8f2d5 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |