المؤلفون: Chantal M. Boulanger, Pierre-Michael Coly

المساهمون: Boulanger, Chantal, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)

المصدر: Journal of Leukocyte Biology
Journal of Leukocyte Biology, Society for Leukocyte Biology, 2022, 111 (1), pp.51-62. ⟨10.1002/JLB.3MIR0221-099R⟩

مصطلحات موضوعية: Inflammation, Senescence, Cell type, Angiogenesis, Immunology, Cell Biology, Biology, Extracellular vesicles, endothelial cells, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cell biology, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Disease Progression, medicine, Animals, Humans, biomarker, Immunology and Allergy, atherosclerosis, medicine.symptom, extracellular vesicles, Lipid bilayer, Cellular Senescence, Intracellular

الوصف: Extracellular vesicles (EVs) are membrane particles released by most cell types in response to different stimuli. They are composed of a lipid bilayer that encloses a wide range of bioactive material, including proteins and nucleic acids. EVs have garnered increasing attention over recent years, as their role in intercellular communication has been brought to light. As such, they have been found to regulate pathophysiologic pathways like inflammation, angiogenesis, or senescence, and are therefore implicated in key aspects atherosclerosis initiation and progression. Interestingly, EVs appear to have a multifaceted role; depending on their cargo, they can either facilitate or hamper the development of atherosclerotic lesions. In this review, we examine how EVs of varying origins may be implicated in the different phases of atherosclerotic lesion development. We also discuss the need to standardize isolation and analysis procedures to fully fulfil their potential as biomarkers and therapeutics for cardiovascular diseases.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::377963f85846d7613c5990becc272544Test
https://doi.org/10.1002/jlb.3mir0221-099rTest

المؤلفون: Jose Garrido-Mesa, Dianne Cooper, Mauro Perretti, Catherine Pickworth, Matthew Golding, Tao Fu, Loïc Rolas, William A. Muller, Lucy M. Collinson, Ezra Aksoy, Maria Gonzalez-Nunez, Mathieu-Benoit Voisin, Thomas D. Nightingale, Natalia Reglero-Real, Laura Vázquez-Martínez, Shani Austin-Williams, Giulia De Rossi, Lorena Pérez-Gutiérrez, Sussan Nourshargh, Chantal M. Boulanger, Sharon A. Tooze, Yoshiaki Kubota, Anna Barkaway, Azumi Yoshimura, Rebeca S. Saleeb

المصدر: Immunity

مصطلحات موضوعية: autophagy, Leukocyte migration, endothelium, Endothelium, PECAM-1, Neutrophils, Immunology, ATG5, ATG16L1, Inflammation, Biology, Article, Mice, 03 medical and health sciences, junctions, 0302 clinical medicine, Leukocyte Trafficking, Human Umbilical Vein Endothelial Cells, medicine, Animals, Humans, Immunology and Allergy, 030304 developmental biology, 0303 health sciences, Cell adhesion molecule, Autophagy, diapedesis, Transendothelial and Transepithelial Migration, Endothelial Cells, Cell migration, 3. Good health, Cell biology, Mice, Inbred C57BL, Chemotaxis, Leukocyte, Intercellular Junctions, Infectious Diseases, medicine.anatomical_structure, Neutrophil Infiltration, medicine.symptom, extravasation, 030217 neurology & neurosurgery

الوصف: Summary The migration of neutrophils from the blood circulation to sites of infection or injury is a key immune response and requires the breaching of endothelial cells (ECs) that line the inner aspect of blood vessels. Unregulated neutrophil transendothelial cell migration (TEM) is pathogenic, but the molecular basis of its physiological termination remains unknown. Here, we demonstrated that ECs of venules in inflamed tissues exhibited a robust autophagic response that was aligned temporally with the peak of neutrophil trafficking and was strictly localized to EC contacts. Genetic ablation of EC autophagy led to excessive neutrophil TEM and uncontrolled leukocyte migration in murine inflammatory models, while pharmacological induction of autophagy suppressed neutrophil infiltration into tissues. Mechanistically, autophagy regulated the remodeling of EC junctions and expression of key EC adhesion molecules, facilitating their intracellular trafficking and degradation. Collectively, we have identified autophagy as a modulator of EC leukocyte trafficking machinery aimed at terminating physiological inflammation.
Graphical abstract
Highlights • Inflamed venular ECs exhibit an autophagic response that localizes to EC contacts • EC ATG5 deficiency promotes excessive and faster neutrophil TEM • Ablation of EC autophagy increases cell surface expression of adhesion molecules • Non-canonical autophagy operates in inflamed ECs and controls neutrophil migration
Transendothelial cell migration (TEM) is a vital step in neutrophil infiltration of tissues, but the molecular basis of its cessation is unclear. Reglero-Real et al. show that in inflamed tissues, endothelial cell autophagy remodels junctional architecture and acts as a negative regulator of neutrophil TEM.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1ee7732ddcf03fd2589976a2b6a36ae5Test
https://doi.org/10.1016/j.immuni.2021.07.012Test

المؤلفون: Michele Geoffrion, Nadiya Khyzha, Katey J. Rayner, Angela Li, Chantal M. Boulanger, My-Anh Nguyen, Myron I. Cybulsky, Andreas Schober, Lei Cai, Mansoor Husain, Eric A. Shikatani, Tong Li, Rickvinder Besla, Ryan E. Temel, Maliheh Nazari-Jahantigh, Henry S. Cheng, Clinton S. Robbins, Jason E. Fish, Zhiqi Chen, Adel Hammoutene, Sonya A. MacParland

المصدر: Circulation Research. 121:354-367

مصطلحات موضوعية: 0301 basic medicine, medicine.medical_specialty, Endothelium, Physiology, medicine.medical_treatment, Cholesterol, VLDL, Bone Marrow Cells, Inflammation, Biology, Article, Mice, 03 medical and health sciences, Internal medicine, medicine, Animals, Mice, Knockout, Bone marrow failure, Endothelial Cells, Hematopoietic stem cell, Atherosclerosis, medicine.disease, 3. Good health, Mice, Inbred C57BL, Endothelial stem cell, MicroRNAs, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Cytokine, Receptors, LDL, LDL receptor, Diet, Atherogenic, Cattle, Bone marrow, medicine.symptom, Cardiology and Cardiovascular Medicine

الوصف: Rationale: Inflammation is a key contributor to atherosclerosis. MicroRNA-146a (miR-146a) has been identified as a critical brake on proinflammatory nuclear factor κ light chain enhancer of activated B cells signaling in several cell types, including endothelial cells and bone marrow (BM)–derived cells. Importantly, miR-146a expression is elevated in human atherosclerotic plaques, and polymorphisms in the miR-146a precursor have been associated with risk of coronary artery disease. Objective: To define the role of endogenous miR-146a during atherogenesis. Methods and Results: Paradoxically, Ldlr −/− (low-density lipoprotein receptor null) mice deficient in miR-146a develop less atherosclerosis, despite having highly elevated levels of circulating proinflammatory cytokines. In contrast, cytokine levels are normalized in Ldlr −/− ;miR-146a −/− mice receiving wild-type BM transplantation, and these mice have enhanced endothelial cell activation and elevated atherosclerotic plaque burden compared with Ldlr −/− mice receiving wild-type BM, demonstrating the atheroprotective role of miR-146a in the endothelium. We find that deficiency of miR-146a in BM-derived cells precipitates defects in hematopoietic stem cell function, contributing to extramedullary hematopoiesis, splenomegaly, BM failure, and decreased levels of circulating proatherogenic cells in mice fed an atherogenic diet. These hematopoietic phenotypes seem to be driven by unrestrained inflammatory signaling that leads to the expansion and eventual exhaustion of hematopoietic cells, and this occurs in the face of lower levels of circulating low-density lipoprotein cholesterol in mice lacking miR-146a in BM-derived cells. Furthermore, we identify sortilin-1( Sort1 ), a known regulator of circulating low-density lipoprotein levels in humans, as a novel target of miR-146a. Conclusions: Our study reveals that miR-146a regulates cholesterol metabolism and tempers chronic inflammatory responses to atherogenic diet by restraining proinflammatory signaling in endothelial cells and BM-derived cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8be7030121afd7044933204a0124939dTest
https://doi.org/10.1161/circresaha.116.310529Test

المؤلفون: Xavier Loyer, Nicolas Amabile, Chantal M. Boulanger, Pierre-Emmanuel Rautou

المساهمون: Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), DHU addressing Unmet Needs through Innovation in hepaTology and gastroenterologY [Paris] (DHU UNITY [APHP]), Institut mutualiste Monsouris (IMM), Boulanger, Chantal

المصدر: Nature Reviews Cardiology
Nature Reviews Cardiology, Nature Publishing Group, 2017, 14 (5), pp.259-272. ⟨10.1038/nrcardio.2017.7⟩

مصطلحات موضوعية: 0301 basic medicine, plaque rupture, Pathology, medicine.medical_specialty, Inflammation, Cell Communication, Coronary Artery Disease, exosomes, 030204 cardiovascular system & hematology, Second Messenger Systems, calcification, Cell therapy, Extracellular Vesicles, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Drug Discovery, medicine, Extracellular, Humans, Lipid bilayer, business.industry, Vesicle, Microvesicles, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cell biology, Cytosol, 030104 developmental biology, biomarker, atherosclerosis, Stem cell, medicine.symptom, Cardiology and Cardiovascular Medicine, business, microvesicles, Biomarkers

الوصف: International audience; Membrane vesicles released in the extracellular space are composed of a lipid bilayer enclosing soluble cytosolic material and nuclear components. Extracellular vesicles include apoptotic bodies, exosomes, and microvesicles (also known previously as microparticles). Originating from different subcellular compartments, the role of extracellular vesicles as regulators of transfer of biological information, acting locally and remotely, is now acknowledged. Circulating vesicles released from platelets, erythrocytes, leukocytes, and endothelial cells contain potential valuable biological information for biomarker discovery in primary and secondary prevention of coronary artery disease. Extracellular vesicles also accumulate in human atherosclerotic plaques, where they affect major biological pathways, including inflammation, proliferation, thrombosis, calcification, and vasoactive responses. Extracellular vesicles also recapitulate the beneficial effect of stem cells to treat cardiac consequences of acute myocardial infarction, and now emerge as an attractive alternative to cell therapy, opening new avenues to vectorize biological information to target tissues. Although interest in microvesicles in the cardiovascular field emerged about 2 decades ago, that for extracellular vesicles, in particular exosomes, started to unfold a decade ago, opening new research and therapeutic avenues. This Review summarizes current knowledge on the role of extracellular vesicles in coronary artery disease, and their emerging potential as biomarkers and therapeutic agents.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0993d3a85c8ef6e8fd5dd071b6e8f896Test
https://doi.org/10.1038/nrcardio.2017.7Test

المؤلفون: Karina Zimmer, Gustavo Campos Ramos, Yong Wang, Ke Xiao, Arne Schmidt, Jan Fiedler, Janet Remke, Stella Marie Reamon-Buettner, Xavier Loyer, Thomas Thum, Andreas Pich, Janika Viereck, Franziska Kenneweg, Mira Jung, Stephane Mazlan, Juliette Nowak, Annette Just, Chantal M. Boulanger, Stefan Frantz, Kai C. Wollert, Lisa Hobuß, Ariana Foinquinos

المساهمون: Publica

المصدر: Journal of molecular and cellular cardiology. 146

مصطلحات موضوعية: 0301 basic medicine, Cardiac function curve, Proteome, Cell Survival, Ischemia, Myocardial Ischemia, Inflammation, 030204 cardiovascular system & hematology, Biology, Vascular Remodeling, Models, Biological, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, medicine, Human Umbilical Vein Endothelial Cells, Animals, Humans, Myocytes, Cardiac, Myocardial infarction, Fibroblast, Molecular Biology, Mice, Knockout, Genetic Pleiotropy, Heart, Extracellular vesicle, Fibroblasts, medicine.disease, female genital diseases and pregnancy complications, Cell biology, Mice, Inbred C57BL, Oxygen, 030104 developmental biology, medicine.anatomical_structure, HEK293 Cells, Gene Expression Regulation, Apoptosis, embryonic structures, Receptors, Calcitriol, RNA, Long Noncoding, medicine.symptom, Cardiology and Cardiovascular Medicine

الوصف: Myocardial ischemia induces a multifaceted remodeling process in the heart. Novel therapeutic entry points to counteract maladaptive signalling include the modulation of non-coding RNA molecules such as long non-coding RNA (lncRNA). We here questioned if the lncRNA candidate H19 exhibits regulatory potential in the setting of myocardial infarction. Initial profiling of H19 expression revealed a dynamic expression profile of H19 with upregulation in the acute phase after murine cardiac ischemia. In vitro, we found that oxygen deficiency leads to H19 upregulation in several cardiac cell types. Repression of endogenous H19 caused multiple phenotypes in cultivated murine cardiomyocytes including enhanced cardiomyocyte apoptosis, at least partly through attenuated vitamin D signalling. Unbiased proteome analysis revealed further involvement of H19 in mRNA splicing and translation as well as inflammatory signalling pathways. To study H19 function more precisely, we investigated the phenotype of systemic H19 loss in a genetic mouse model of H19 deletion (H19 KO). Infarcted heart tissue of H19 KO mice showed a massive increase of pro-inflammatory cytokines after ischemia-reperfusion injury (I/R) without significant effects on scar formation or cardiac function but exaggerated cardiac hypertrophy indicating pathological cardiac remodeling. H19-dependent changes in cardiomyocyte-derived extracellular vesicle release and alterations in NF-κB signalling were evident. Cardiac cell fractionation experiments revealed that enhanced H19 expression in the proliferative phase after MI derived mainly from cardiac fibroblasts. Here further research is needed to elucidate its role in fibroblast activation and function. In conclusion, the lncRNA H19 is dynamically regulated after MI and involved in multiple pathways of different cardiac cell types including cardiomyocyte apoptosis and cardiac inflammation.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::de73c3915ef8c66118970f3cfd5c56ddTest
https://pubmed.ncbi.nlm.nih.gov/32649928Test

المؤلفون: Pierre-Michael Coly, Chantal M. Boulanger

المساهمون: Boulanger, Chantal, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)

المصدر: Circulation Research
Circulation Research, American Heart Association, 2019, 125 (1), pp.53-54. ⟨10.1161/CIRCRESAHA.119.315328⟩

مصطلحات موضوعية: Physiology, Chemistry, endotoxemia, Vesicle, Inflammation, Mitochondrion, Extracellular vesicles, endothelial cells, Cell biology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, mitochondria, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, inflammation, Extracellular, medicine, medicine.symptom, Cardiology and Cardiovascular Medicine, ComputingMilieux_MISCELLANEOUS

الوصف: International audience; No abstract available

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5078c85e4b11fc75cc5a7f9087051890Test
https://www.hal.inserm.fr/inserm-03620396Test

المؤلفون: Chantal M. Boulanger, Fabrice Cognasse, Ming Li Chou, Jerard Seghatchian, Sandrine Laradi, Thierry Burnouf, Hind Hamzeh-Cognasse, Olivier Garraud, Nicolas Amabile

المصدر: Transfusion and Apheresis Science. 53:159-167

مصطلحات موضوعية: Chemokine, Lipid Bilayers, Blood Component Transfusion, Inflammation, chemistry.chemical_compound, Cell-Derived Microparticles, Animals, Humans, Medicine, Platelet, Lipid bilayer, Cytoskeleton, Blood Cells, biology, business.industry, Cholesterol, Vesicle, Endothelial Cells, Membrane Proteins, Hematology, Adhesion, Cell biology, chemistry, Immunology, biology.protein, medicine.symptom, business, Intracellular

الوصف: Microparticles are small membrane-bound vesicles found in body fluids including peripheral blood. Microparticles are an intrinsic part of blood labile products delivered to transfused patients and have active roles in inflammation. They are delimited by a lipid bilayer composed mainly of phospholipids, cholesterol, membrane-associated proteins, intracellular components such as metabolic enzymes, proteins-involved in adhesion and fusion, cytoskeletal-associated proteins, surface glycoproteins and/or chemokines. Microparticles can trigger a pro-inflammatory message to neighbouring or target cells. Microparticles originating from platelets, leukocytes, erythrocytes, and endothelial cells are associated with a variety of pathophysiological conditions. This review summarises the role of Microparticles in modulating inflammation.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::88daaea4af55cdb0f1526a99b158f0e9Test
https://doi.org/10.1016/j.transci.2015.10.013Test

المؤلفون: Min Yin, Xavier Loyer, Chantal M. Boulanger

المصدر: European Journal of Pharmacology. 763:90-103

مصطلحات موضوعية: Pharmacology, Cell type, Biological Transport, Inflammation, Cell Communication, Extracellular vesicle, Biology, Atherosclerosis, medicine.disease, Phenotype, Microvesicles, Cell biology, Extracellular Vesicles, Drug delivery, medicine, Animals, Humans, Molecular Targeted Therapy, medicine.symptom, Endothelial dysfunction, Function (biology)

الوصف: Extracellular vesicles released by most cell types, include apoptotic bodies (ABs), microvesicles (MVs) and exosomes. They play a crucial role in physiology and pathology, contributing to "cell-to-cell" communication by modifying the phenotype and the function of target cells. Thus, extracellular vesicles participate in the key processes of atherosclerosis from endothelial dysfunction, vascular wall inflammation to vascular remodeling. The purpose of this review is to summarize recent findings on extracellular vesicle formation, structure, release and clearance. We focus on the deleterious and beneficial effects of extracellular vesicles in the development of atherosclerosis. The potential role of extracellular vesicles as biomarkers and pharmacological targets, their innate therapeutic capacity, or their use for novel drug delivery devices in atherosclerotic cardiovascular diseases will also be discussed.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7a524248130213634de06020f8e16c40Test
https://doi.org/10.1016/j.ejphar.2015.06.047Test

المؤلفون: Johanna Busse, Juliette Lasselin, Benoit Viollet, Xavier Loyer, Alain Tedgui, Patrice Codogno, Marouane Kheloufi, Johanne Poisson, Michele Souyri, Pierre Julia, Nicolas Dupont, Isabelle Pic, Konstantin Stark, Cécile Devue, Abdul I. Barakat, Anne-Clémence Vion, Adel Hammoutene, Julie Lafaurie-Janvore, Chantal M. Boulanger, Pierre-Emmanuel Rautou

المساهمون: Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Klinikum der Universität [München], Laboratoire d'hydrodynamique (LadHyX), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Hématopoïèse normale et pathologique : émergence, environnement et recherche translationnelle [Paris] ((UMR_S1131 / U1131)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Vion, Anne-clemence, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)

المصدر: Proceedings of the National Academy of Sciences of the United States of America
Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2017, 114 (41), pp.E8675-E8684. ⟨10.1073/pnas.1702223114⟩
Proceedings of the National Academy of Sciences of the United States of America, 2017, 114 (41), pp.E8675-E8684. ⟨10.1073/pnas.1702223114⟩

مصطلحات موضوعية: Male, 0301 basic medicine, Senescence, autophagy, Hypercholesterolemia, Cellular homeostasis, Apoptosis, Mice, Transgenic, Inflammation, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 030204 cardiovascular system & hematology, Biology, shear stress, Proinflammatory cytokine, Mice, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Stress, Physiological, endothelial, Human Umbilical Vein Endothelial Cells, medicine, Animals, Humans, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Cellular Senescence, PI3K/AKT/mTOR pathway, Multidisciplinary, Autophagy, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Cell biology, Mice, Inbred C57BL, Endothelial stem cell, 030104 developmental biology, PNAS Plus, inflammation, Female, atherosclerosis, medicine.symptom

الوصف: International audience; It has been known for some time that atherosclerotic lesions preferentially develop in areas exposed to low SS and are characterized by a proinflammatory, apoptotic, and senescent endothelial phenotype. Conversely, areas exposed to high SS are protected from plaque development, but the mechanisms have remained elusive. Autophagy is a protective mechanism that allows recycling of defective organelles and proteins to maintain cellular homeostasis. We aimed to understand the role of endothelial autophagy in the atheroprotective effect of high SS. Atheroprotective high SS stimulated endothelial autophagic flux in human and murine arteries. On the contrary, endothelial cells exposed to atheroprone low SS were characterized by inefficient autophagy as a result of mammalian target of rapamycin (mTOR) activation, AMPKα inhibition, and blockade of the autophagic flux. In hypercholesterolemic mice, deficiency in endothelial autophagy increased plaque burden only in the atheroresistant areas exposed to high SS; plaque size was unchanged in atheroprone areas, in which endothelial autophagy flux is already blocked. In cultured cells and in transgenic mice, deficiency in endothelial autophagy was characterized by defects in endothelial alignment with flow direction, a hallmark of endothelial cell health. This effect was associated with an increase in endothelial apoptosis and senescence in high-SS regions. Deficiency in endothelial autophagy also increased TNF-α-induced inflammation under high-SS conditions and decreased expression of the antiinflammatory factor KLF-2. Altogether, these results show that adequate endothelial autophagic flux under high SS limits atherosclerotic plaque formation by preventing endothelial apoptosis, senescence, and inflammation.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::25b01f6e6b7622c1bc0a495874f6d4fdTest
https://doi.org/10.1073/pnas.1702223114Test

المؤلفون: Ziad Mallat, Chantal M. Boulanger, Alain Tedgui, Xavier Loyer

المصدر: Expert Opinion on Therapeutic Targets. 19:489-496

مصطلحات موضوعية: Cell type, Endothelium, Clinical Biochemistry, Cell, Inflammation, Biology, chemistry.chemical_compound, Drug Discovery, microRNA, Gene expression, medicine, Animals, Humans, Antagomir, RNA Processing, Post-Transcriptional, Pharmacology, Endothelial Cells, Atherosclerosis, Phenotype, Disease Models, Animal, MicroRNAs, medicine.anatomical_structure, Gene Expression Regulation, chemistry, Drug Design, Immunology, Disease Progression, Cancer research, Molecular Medicine, medicine.symptom

الوصف: Atherosclerosis is a chronic inflammatory disease of the arterial wall. A number of phenotypic cell changes occur during the development and progression of atherosclerosis. MicroRNAs (miRNAs) are key regulators of gene expression that act at the post-transcriptional level. They have been implicated in cardiovascular diseases, including atherosclerosis.This review provides an overview of our knowledge about the expression and the roles of miRNAs in different cell types involved in atherosclerosis, with a focus on experimental strategies to modulate miRNA expression and their therapeutic effects in animal models of atherosclerosis. miRNA expression is regulated by inflammatory conditions and by shear stress in endothelial cells. Therapeutic approaches using antagomiR and miRNA mimic delivery and have been shown potentially effective in atherosclerosis. Moreover, a large body of evidence exists supporting a role for not only intracellular miRNA, but also miRNA carried by extracellular vesicles that are involved in inter-cellular communication through the transfer of miRNA.Modulation of miRNA expression could represent novel innovative therapeutic approaches to treat atherosclerosis by targeting a single cell type or specific pathways. Future challenges will consist in deciphering the mechanisms involved in miRNA regulation and in improving cell-specific delivery of 'miR-drugs' by alternative strategies, including miRNA-enriched micro vesicles.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5b0589176e030b7b0ae4204eadda691dTest
https://doi.org/10.1517/14728222.2014.989835Test