Laboratoire de recherche vasculaire translationnelle
Présentation
Le Laboratoire de Recherche Vasculaire Translationnelle (Laboratory for Vascular Translational Science - LVTS) est associé à l’Inserm, à l’Université Paris Diderot, et l’Université Paris 13. Il est identifié comme UMRS 1148.
Avec 5 équipes, le laboratoire d’environ 150 personnes a une approche transdisciplinaire avec les objectifs de lutte contre les pathologies vasculaires. Les équipes sont affiliées à 3 ITMO (CMN, TS, IHP), à plusieurs Ecoles doctorales du PRES Sorbonne Paris Cité, et à 2 sections scientifiques de l'Inserm (CSS4 et CSS8).
Pour mener à bien ces projets, les compétences humaines et technologiques comprennent les bases de données cliniques, enquêtes cliniques translationnelles (sténose carotidienne, anévrisme et dissections de l'aorte ascendante, Biocore ), bases de données de tissus humains et de cellules, de nombreux modèles expérimentaux de la maladie (souris transgéniques, rats , lapins), des méthodes de biologie moléculaire et cellulaire (génétique et épigénétique, protéomique, ingénierie des protéines, cytométrie en flux), la chimie des biopolymères, l’élaboration de biomatériaux et nanosystèmes, et les technologies d'imagerie chez les petits animaux et chez l'homme (imagerie nucléaire, ultrasons et IRM).
Equipes de recherche
Le projet est structuré en 5 équipes. Les objectifs mettent en évidence la complémentarité des équipes et des interfaces existantes autour d'un thème structurant sur le coeur et les vaisseaux.
- Equipe 1 : " Biologie de l'athérothrombose" (chef d'équipe : A Nicoletti) - voir aussi l'UFR Sciences du Vivant
- Equipe 2 : "Maladies structurelles cardiovasculaires" (chef d'équipe : C Boileau & G Jondeau)
- Equipe 3 : "Bio-ingénierie cardiovasculaire" (chef d'équipe : D Letourneur)
- Equipe 4 : " Imagerie cardiovasculaire" (chef d'équipe : D Le Guludec)
- Equipe 5 : "Maladies athérothrombotiques du coeur et du cerveau" (chef d'équipe : G Steg)
[hal-01414463] CLOSE: Closure of patent foramen ovale, oral anticoagulants or antiplatelet therapy to prevent stroke recurrence: Study design
Date: 12 Dec 2016 - 12:44
Desc: Rationale Currently available data do not provide definitive evidence on the comparative benefits of closure of patent foramen ovale, oral anticoagulants and antiplatelet therapy in patients with patent foramen ovale-associated cryptogenic stroke Aim To assess whether transcatheter patent foramen ovale closure plus antiplatelet therapy is superior to antiplatelet therapy alone and whether oral anticoagulant therapy is superior to antiplatelet therapy, for secondary stroke prevention in patients aged 16 to 60 years with a large patent foramen ovale or a patent foramen ovale associated with an atrial septal aneurysm, and an otherwise unexplained ischaemic stroke or retinal ischaemia. Sample size Six hundred and sixty-four patients were included in the study. Methods and design CLOSE is an academic-driven, multicentre, randomized, open-label, three-group, superiority trial with blinded adjudication of outcome events. The trial has been registered with Clinical Trials Register (Clinicaltrials.gov, NCT00562289). Patient recruitment started in December 2007. Patient follow-up will continue until December 2016. Expected mean follow-up=5.6 years. Study outcomes The primary efficacy outcome is the occurrence of fatal or nonfatal stroke. Safety outcomes include fatal, life-threatening or major procedure- or device-related complications and fatal, life-threatening or major haemorrhagic complications. Discussion CLOSE is the first specifically designed trial to assess the superiority of patent foramen ovale closure over antiplatelet therapy alone and the superiority of oral anticoagulants over antiplatelet therapy to prevent stroke recurrence in patients with patent foramen ovale-associated cryptogenic stroke.
[halshs-02299010] Neandertal and Denisovan DNA from Pleistocene sediments
Date: 27 Sep 2019 - 14:31
Desc: * Although a rich record of Pleistocene human-associated archaeological assemblages exists, the scarcity of hominin fossils often impedes the understanding of which hominins occupied a site. Using targeted enrichment of mitochondrial DNA, we show that cave sediments represent a rich source of ancient mammalian DNA that often includes traces of hominin DNA, even at sites and in layers where no hominin remains have been discovered. By automation-assisted screening of numerous sediment samples, we detected Neandertal DNA in eight archaeological layers from four caves in Eurasia. In Denisova Cave, we retrieved Denisovan DNA in a Middle Pleistocene layer near the bottom of the stratigraphy. Our work opens the possibility of detecting the presence of hominin groups at sites and in areas where no skeletal remains are found.
[hal-03408859] The apparent mechanical effect of isolated amyloid‐β and α‐synuclein aggregates revealed by multi‐frequency MRE
Date: 24 Nov 2023 - 18:20
Desc: Several biological processes are involved in dementia, and fibrillar aggregation of misshaped endogenous proteins appears to be an early hallmark of neurodegenerative disease. A recently developed means of studying neurodegenerative diseases is magnetic resonance elastography (MRE), an imaging technique investigating the mechanical properties of tissues. Although mechanical changes associated with these diseases have been detected, the specific signal of fibrils has not yet been isolated in clinical or preclinical studies. The current study aims to exploit the fractal‐like properties of fibrils to separate them from nonaggregated proteins using a multi‐frequency MRE power law exponent in a phantom study. Two types of fibril, α‐synuclein (α‐Syn) and amyloid‐β (Aβ), and a nonaggregated protein, bovine serum albumin, used as control, were incorporated in a dedicated nondispersive agarose phantom. Elastography was performed at multiple frequencies between 400 and 1200 Hz. After 3D‐direct inversion, storage modulus (G'), phase angle (ϕ), wave speed and the power law exponent (y) were computed. No significant changes in G' and ϕ were detected. Both α‐Syn and Aβ inclusions showed significantly higher y values than control inclusions ( P = 0.005) but did not differ between each other. The current phantom study highlighted a specific biomechanical effect of α‐Syn and Aβ aggregates, which was better captured with the power law exponent derived from multi‐frequency MRE than with single frequency‐derived parameters.
[hal-02442441] Comparative analysis of nanosystems' effects on human endothelial and monocytic cell functions.
Date: 16 Jan 2020 - 14:24
Desc: The objective of our work was to investigate the effects of different types of nanoparticles on endothelial (HUVEC) and monocytic cell functions. We prepared and tested 14 different nanosystems comprising liposomes, lipid nanoparticles, polymer, and iron oxide nanoparticles. Some of the tested nanosystems contained targeting, therapeutic, or contrast agent(s). The effect of particles (0-400 mu g/mL) on endothelial-monocytic cell interactions in response to TNF-alpha was investigated using an arterial bifurcation model and dynamic monocyte adhesion assay. Spontaneous HUVEC migration (0-100 mu g/mL nanoparticles) and chemotaxis of monocytic cells towards MCP-1 in presence of particles (0-400 mu g/mL) were determined using a barrier assay and a modified Boyden chamber assay, respectively. Lipid nanoparticles dose-dependently reduced monocytic cell chemotaxis and adhesion to activated HUVECs. Liposomal nanoparticles had little effect on cell migration, but one formulation induced monocytic cell recruitment by HUVECs under non-uniform shear stress by about 50%. Fucoidan-coated polymer nanoparticles (25-50 mu g/mL) inhibited HUVEC migration and monocytic cell chemotaxis, and had a suppressive effect on monocytic cell recruitment under non-uniform shear stress. No significant effects of iron oxide nanoparticles on monocytic cell recruitment were observed except lauric acid and human albumin-coated particles which increased endothelial-monocytic interactions by 60-70%. Some of the iron oxide nanoparticles inhibited HUVEC migration and monocytic cell chemotaxis. These nanoparticle-induced effects are of importance for vascular cell biology and function and must be considered before the potential clinical use of some of the analyzed nanosystems in cardiovascular applications.
[hal-02438543] From design to the clinic: practical guidelines for translating cardiovascular nanomedicine
Date: 16 Jan 2020 - 11:55
Desc: [...]
Autres contacts
U.F.R. de Médecine Paris Diderot (site Xavier-Bichat)
U698 Inserm - CHU Xavier Bichat
16, rue Henri-Huchard - B.P. 416
75877 PARIS CEDEX 18