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 12 月 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.
[hal-02966416] Insights into Species Preservation: Cryobanking of Rabbit Somatic and Pluripotent Stem Cells
Date: 14 10 月 2020 - 01:04
Desc: Induced pluripotent stem cells (iPSCs) are obtained by genetically reprogramming adult somatic cells via the overexpression of specific pluripotent genes. The resulting cells possess the same differentiation properties as blastocyst-stage embryonic stem cells (ESCs) and can be used to produce new individuals by embryonic complementation, nuclear transfer cloning, or in vitro fertilization after differentiation into male or female gametes. Therefore, iPSCs are highly valuable for preserving biodiversity and, together with somatic cells, can enlarge the pool of reproductive samples for cryobanking. In this study, we subjected rabbit iPSCs (rbiPSCs) and rabbit ear tissues to several cryopreservation conditions with the aim of defining safe and non-toxic slow-freezing protocols. We compared a commercial synthetic medium (STEM ALPHA.CRYO3) with a biological medium based on fetal bovine serum (FBS) together with low (0-5%) and high (10%) concentrations of dimethyl sulfoxide (DMSO). Our data demonstrated the efficacy of a CRYO3-based medium containing 4% DMSO for the cryopreservation of skin tissues and rbiPSCs. Specifically, this medium provided similar or even better biological results than the commonly used freezing medium composed of FBS and 10% DMSO. The results of this study therefore represent an encouraging first step towards the use of iPSCs for species preservation.
[hal-02450391] Laparoscopic insemination method in sheep allows the use of an animal protein-free and inexpensive freezing medium
Date: 22 1 月 2020 - 22:12
Desc: Animal-derived products are widely used in sperm cryopreservation for their cryoprotective properties. These components, however, must be replaced because of sanitary risks. STEMALPHA.CRYO3 (Ref. 5617, Stem Alpha), called CRYO3, is a chemically defined preservation medium currently used for freezing human tissue and adult stem cells. The aim of this study was to evaluate the effects of a CRYO3-based medium and of two cooling rates on in vitro parameters and in vivo fertility of ram sperm. Six rams (Blanche du Massif Central) were subjected to sperm collection four times using an artificial vagina. Sperm were split and frozen in three media: an egg yolk and milk-based medium (positive control), a CRYO3-based medium (tested medium), and a medium without additives (negative control). The two cooling rates were related to the distance between the straws and the surface of liquid nitrogen during the freezing process (5 and 20 cm). Sperm membrane integrity (propidium iodide/SYBR-14), acrosome integrity (fluorescein isothiocyanate-peanut agglutinin/propidium iodide; FITC-PNA/PI), and mitochondrial membrane potential (JC-1) were assessed using flow cytometry, whereas functional membrane integrity was assessed using a hypo-osmotic swelling test and motion characteristics were evaluated using computer-assisted sperm analysis. Pregnancy rate, parturition rate, and prolificacy were evaluated after performing laparoscopic inseminations (n ¼ 75 ewes). Moreover, we characterised the freezing media thermodynamically using a differential scanning calorimeter. Statistical analyses were performed using R software. In vitro parameters were assessed using a mixed model including the time and the medium as fixed effects and the ram as a random effect. Pregnancy and parturition rates, following a binomial distribution, and prolificacy, assumed to follow a Poisson distribution, were analysed using generalised linear models, including the medium as a fixed effect and the ram as a random effect. Differences with P , 0.05 were considered statistically significant. The cooling rates had no significant effect except on the wobble motion parameter. The positive control medium showed significantly higher results than the CRYO3-based medium and the negative control medium for all in vitro parameters except for straightness motion parameter. Conversely, field trials showed no significant difference between the media for pregnancy rate (71, 64, and 74%), parturition rate (68, 61, and 74%) and prolificacy (2.0, 2.1, and 1.7), for the positive control, CRYO3-based medium, and the negative control, respectively. This study showed that the product, CRYO3, cannot replace egg yolk and milk in freezing extenders. Moreover, we showed that laparoscopic inseminations allowed a 74% parturition rate due to an easy and inexpensive medium comprising only a Tris buffer and glycerol. Although it could not be used on a large scale, this medium remains an option for international transport or long-term storage of genetic diversity.
[hal-01813449] Editor’s Choice-Medically managed patients with non–ST-elevation acute myocardial infarction have heterogeneous outcomes, based on performance of angiography and extent of coronary artery disease
Date: 12 6 月 2018 - 14:40
Desc: BACKGROUND: Medically managed individuals represent a high-risk group among patients with non-ST-elevation acute myocardial infarction (NSTE-AMI). We hypothesized that prognosis in this group is heterogeneous, depending on whether medical management was decided with or without coronary angiography (CAG). METHODS: Using data from the French Registry of Acute ST-Elevation or Non-ST-Elevation Myocardial Infarction (FAST-MI), we analysed data from 798 patients with NSTE-AMI who were medically managed (i.e. without revascularization during the index hospitalization). Patients were categorized according to the performance of CAG and, if performed, to the extent of coronary artery disease (CAD). RESULTS: There were marked differences in baseline demographics, according to whether CAG was performed and to the extent of CAD. While the overall mortality rate at five years was high (56.2%), it differed greatly between groups, with patients who did not undergo CAG having a higher mortality rate (77.4%) than patients who underwent CAG (36.7%, p<0.001), and a higher mortality rate even than patients with multivessel CAD (54.2%, p<0.001). By multivariable analysis, non-performance of CAG was an independent predictor of all-cause mortality among medically managed NSTE-AMI patients (adjusted hazard ratios (95% confidence intervals) 3.19 (1.79-5.67) at 30 days, 2.28 (1.60-3.26) at one year, and 1.63 (1.28-2.07) at five years; all p<0.001). CONCLUSION: Medically managed patients with NSTE-AMI are a heterogeneous group in terms of baseline characteristics and outcomes. The highest risk patients are those who do not undergo CAG. Non-performance of CAG is a strong predictor of death. (FAST-MI, NCT00673036).
[hal-01996274] High burden of recurrent cardiovascular events in heterozygous familial hypercholesterolemia: The French Familial Hypercholesterolemia Registry
Date: 1 2 月 2019 - 19:11
Desc: Background and aims: Cardiovascular risk is high in heterozygous familial hypercholesterolemia (HeFH). The objective of this study was to describe recurrent cardiovascular events in selected patients with HeFH attending lipid clinics in France. Methods: We included 781 patients with a clinical (Dutch Lipid Clinic Network score >= 6) or genetic diagnosis of HeFH who had experienced a first cardiovascular event (myocardial infarction, percutaneous coronary intervention or coronary bypass, unstable angina, stroke, peripheral arterial revascularization or cardiovascular death) and were enrolled in the French Familial Hypercholesterolemia Registry (November 2015 to March 2018). Results: The first cardiovascular event occurred at the mean age of 47 years (interquartile range 39-55) in a predominantly male population (72%); 48% of patients were on statin therapy. Overall, 37% of patients had at least one recurrent cardiovascular event (mean of 1.8 events per patient), of which 32% occurred in the 12 months after the index event; 55% of events occurred > 3 years after the first event. Mean LDL-C at the last clinic visit was 144 +/- 75 mg/dL (132 +/- 69 mg/dL for patients on high-potency statin therapy and 223 +/- 85 mg/dL for untreated patients). Conclusions: The rate of recurrent cardiovascular events was high in French patients with HeFH in secondary prevention. The detection of FH during childhood is crucial to prevent CV events at a young age by early initiating statin therapy. There is a clear urgent need to expand the actual very small target population which can be treated with the PCSK9 inhibitor in France.
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