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-03580779] Drug-induced aortic valve stenosis: An under recognized entity
Date: 18 fév 2022 - 17:19
Desc: Background: We have been intrigued by the observation that aortic stenosis (AS) may be associated with characteristic features of mitral drug-induced valvular heart disease (DI-VHD) in patients exposed to valvulopathic drugs, thus suggesting that beyond restrictive heart valve regurgitation, valvulopathic drugs may be involved in the pathogenesis of AS. Methods: Herein are reported echocardiographic features, and pathological findings encountered in a series of patients suffering from both AS (mean gradient > 15 mm Hg) and mitral DI-VHD after valvulopathic drugs exposure. History of rheumatic fever, chest radiation therapy, systemic disease or bicuspid aortic valve disease were exclusion criteria. Results: Twenty-five (19 females, mean age 62 years) patients having both AS and typical features of mitral DI-VHD were identified. Mean transaortic pressure gradient was 32+/-13 mm Hg. Aortic regurgitation was >= mild in 24 (96%) but trivial in one. Known history of aortic valve regurgitation following drug initiation prior the development of AS was previously diagnosed in 17 patients (68%). Six patients underwent aortic valve replacement and 3 both aortic and mitral valve replacement. In the 9 patients with pathology analysis, aortic valvular endocardium was markedly thickened by dense non-inflammatory fibrosis, a characteristic feature of DI-VHD. Conclusion: The association between AS and typical mitral DI-VHD after valvulopathic drug exposure may not be fortuitous. Aortic regurgitation was usually associated to AS and preceded AS in most cases but may be lacking. Pathology demonstrated the potential role of valvulopathic drugs in the development of AS. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
[hal-01447065] Eradication of Hepatitis C Virus Infection in Patients With Cirrhosis Reduces Risk of Liver and Non-Liver Complications
Date: 26 jan 2017 - 15:29
Desc: BACKGROUND & AIMS: We performed a prospective study to investigate the effects of a sustained viral response (SVR) on outcomes of patients with hepatitis C virus (HCV) infection and compensated cirrhosis. METHODS: We collected data from 1323 patients included in the prospective Agence Nationale pour la Recherche sur le SIDA et les hépatites virales (ANRS) viral cirrhosis (CirVir) cohort, recruited from 35 clinical centers in France from 2006 through 2012. All patients had HCV infection and biopsy-proven cirrhosis, were Child-Pugh class A, and had no prior liver complications. All patients received anti-HCV treatment before or after inclusion (with interferon then with direct antiviral agents) and underwent an ultrasound examination every 6 months, as well as endoscopic evaluations. SVR was considered as a time-dependent covariate; its effect on outcome was assessed by the Cox proportional hazard regression method. We used a propensity score to minimize confounding by indication of treatment and capacity to achieve SVR. RESULTS: After a median follow-up period of 58.2 months, 668 patients (50.5%) achieved SVR. SVR was associated with a decreased incidence of hepatocellular carcinoma (hazard ratio [HR] compared with patients without an SVR, 0.29; 95% confidence interval [CI], 0.19-0.43; P < .001) and hepatic decompensation (HR, 0.26; 95% CI, 0.17-0.39; P < .001). Patients with SVRs also had a lower risk of cardiovascular events (HR, 0.42; 95% CI, 0.25-0.69; P = .001) and bacterial infections (HR, 0.44; 95% CI, 0.29-0.68; P < .001). Metabolic features were associated with a higher risk of hepatocellular carcinoma in patients with SVRs, but not in patients with viremia. SVR affected overall mortality (HR, 0.27 compared with patients without SVR; 95% CI, 0.18-0.42; P < .001) and death from liver-related and non-liver-related causes. Similar results were obtained in a propensity score-matched population. CONCLUSIONS: We confirmed a reduction in critical events, liver-related or not, in a prospective study of patients with HCV infection and compensated cirrhosis included in the CirVir cohort who achieved an SVR. We found an SVR to reduce overall mortality and risk of death from liver-related and non-liver-related causes. A longer follow-up evaluation is required to accurately describe and assess specific risk factors for complications in this population.
[inserm-01847283] Evaluation of Functionalized Polysaccharide Microparticles Dosimetry for SPECT Imaging Based on Biodistribution Data of Rats
Date: 23 juil 2018 - 15:28
Desc: Purpose: Technetium-99 m (Tc-99 m)-labelled microparticles, functionalized with fucoidan to present a high affinity for P-Selectin, or [ 99m Tc] MP-fucoidan, were developed as a novel SPECT radiotracer for abdominal aortic aneurysm (AAA). As a prerequisite step forwards a clinical trial, the biodistribution and dosimetry of these [ 99m Tc] MP-fucoidan microparticles were performed in rats in order to estimate the absorbed and effective dose in humans. Procedures: Microparticles with a maximum hydrodynamic diameter of 4 μm were obtained by crosslinking polysaccharides dextran and pullulan. They were functionalized with fucoidan then radiolabelled with Tc-99 m. A mean labelling efficiency of 92±1 % was measured. [ 99m Tc] MP-fucoidan (43±2 MBq) was injected to 24 rats via the penis vein. Rats were euthanized at 30, 60, 120 and 240 min after injection (4 rats at each time point). Samples of each organ, as well as the injected microparticle suspensions, were aliquoted for counting. Four animals were sacrificed for blood clearance studies and four were sacrificed for image analysis and quantification of the cortical, medullary, papillary kidney, and pelvis uptake. A compartmental model was realised using SAAM II and organ data were fitted. The area under the curve was then used to compute the residence times in each rat organs and converted to human residence time values. Absorbed and effective human doses in organs were estimated using (1) the OLINDA/EXM 1.1 software with the hermaphroditic mathematical phantoms and (2) the OEDIPE software associated to the MCNPX Monte Carlo code and the ICRP reference computational male and female phantoms, using the updated tissue weighting factors in the ICRP Publication 103. Results: The highest human residence times were found in the liver, kidneys, and urinary bladder wall. The largest doses were found in the kidneys and then in the urinary bladder wall and liver. The human effective doses were 6.06 μSv/MBq for the hermaphroditic mathematical phantom and 5.95 μSv/MBq for the ICRP adult reference computational phantom. Conclusions: Animal-based human dose estimates support a future first-inhuman testing of [ 99m Tc] MP-fucoidan following IV injection.
[inserm-01844657] Pro-angiogenic effect of RANTES-loaded polysaccharide-based microparticles for a mouse ischemia therapy
Date: 19 juil 2018 - 16:36
Desc: Peripheral arterial disease results from the chronic obstruction of arteries leading to critical hindlimb ischemia. The aim was to develop a new therapeutic strategy of revascularization by using biodegradable and biocompatible polysaccharides-based microparticles (MP) to treat the mouse hindlimb ischemia. For this purpose, we deliver the pro-angiogenic chemokine Regulated upon Activation, Normal T-cell Expressed and Secreted (RANTES)/CCL5 in the mouse ischemic hindlimb, in solution or incorporated into polysaccharide-based microparticles. We demonstrate that RANTES-loaded microparticles improve the clinical score, induce the revascularization and the muscle regeneration in injured mice limb. To decipher the mechanisms underlying RANTES effects in vivo, we demonstrate that RANTES increases the spreading, the migration of human endothelial progenitor cells (EPC) and the formation of vascular network. The main receptors of RANTES i.e. CCR5, syndecan-4 and CD44 expressed at endothelial progenitor cell surface are involved in RANTES-induced in vitro biological effects on EPC. By using two RANTES mutants, [E66A]-RANTES with impaired ability to oligomerize, and [44 AANA 47]-RANTES mutated in the main RANTES-glycosaminoglycan binding site, we demonstrate that both chemokine oligomerization and binding site to glycosaminoglycans are essential for RANTES-induced angiogenesis in vitro. Herein we improved the muscle regeneration and revascularization after RANTES-loaded MP local injection in mice hindlimb ischemia.
[hal-01945068] Anti– N -Methyl- d -Aspartate Receptor Encephalitis in Adult Patients Requiring Intensive Care
Date: 5 déc 2018 - 10:11
Desc: RATIONALE: Encephalitis caused by anti-N-methyl-d-aspartate receptor (NMDAR) antibodies is the leading cause of immune-mediated encephalitis. There are limited data on intensive care unit (ICU) management of these patients. OBJECTIVES: To identify prognostic factors of good neurologic outcome in patients admitted to an ICU with anti-NMDAR encephalitis. METHODS: This was an observational multicenter study of all consecutive adult patients diagnosed with anti-NMDAR encephalitis at the French National Reference Centre, admitted to an ICU between 2008 and 2014. The primary outcome was a good neurologic outcome at 6 months after ICU admission, defined by a modified Rankin Scale score of 0-2. MEASUREMENTS AND MAIN RESULTS: Seventy-seven patients were included from 52 ICUs. First-line immunotherapy consisted of steroids (n = 61/74; 82%), intravenous immunoglobulins (n = 71/74; 96%), and plasmapheresis (n = 17/74; 23%). Forty-five (61%) patients received second-line immunotherapy (cyclophosphamide, rituximab, or both). At 6 months, 57% of patients had a good neurologic outcome. Independent factors of good neurologic outcome were early (≤8 d after ICU admission) immunotherapy (odds ratio, 16.16; 95% confidence interval, 3.32-78.64; for combined first-line immunotherapy with steroids and intravenous immunoglobulins vs. late immunotherapy), and a low white blood cell count on the first cerebrospinal examination (odds ratio, 9.83 for <5 vs. >50 cells/mm3; 95% confidence interval, 1.07-90.65). Presence of nonneurologic organ failures at ICU admission and occurrence of status epilepticus during ICU stay were not associated with neurologic outcome. CONCLUSIONS: The prognosis of adult patients with anti-NMDAR encephalitis requiring intensive care is good, especially when immunotherapy is initiated early, advocating for prompt diagnosis and early aggressive treatment.
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