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-02148522] Palladium-loaded cucurbit[7]uril-modified iron oxide nanoparticles for C-C cross-coupling reactions
Date: 9 avr 2021 - 04:31
Desc: [...]
[inserm-02438278] Plasminogen Activator Inhibitor-1 (PAI-1) deficiency predisposes to depression and resistance to treatments
Date: 8 avr 2021 - 19:14
Desc: Major depressive disorder (MDD) is one of the most frequent psychiatric illnesses, leading to reduced quality of life, ability to work and sociability, thus ranking among the major causes of disability and morbidity worldwide. To date, genetic and environmental determinants of MDD remain mostly unknown. Here, we investigated whether and how the Plasminogen Activator Inhibitor-1 (PAI-1) may contribute to MDD. We first examined the phenotype of PAI-1 knockout (PAI-1-/-) and wild-type (PAI-1+/+) male mice with a range of behavioral tests assessing depressive-like behaviors (n = 276). We next investigated the mechanisms relating PAI-1 to MDD using molecular, biochemical and pharmacological analyzes. We demonstrate here that PAI-1 plays a key role in depression by a mechanism independent of the tissue-type Plasminogen Activator (tPA) - Brain-Derived Neurotrophic Factor (BDNF) axis, but associated with impaired metabolisms of serotonin and dopamine. Our data also reveal that PAI-1 interferes with therapeutic responses to selective serotonin reuptake inhibitors (escitalopram, fluoxetine). We thus highlight a new genetic preclinical model of depression, with the lack of PAI-1 as a factor of predisposition to MDD. Altogether, these original data reveal that PAI-1 should be now considered as a key player of MDD and as a potential target for the development of new drugs to cure depressive patients resistant to current treatments.
[hal-01447065] Eradication of Hepatitis C Virus Infection in Patients With Cirrhosis Reduces Risk of Liver and Non-Liver Complications
Date: 8 avr 2021 - 15:21
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.
[cea-01857264] GraftFast Surface Engineering to Improve MOF Nanoparticles Furtiveness
Date: 8 avr 2021 - 04:41
Desc: Controlling the outer surface of nanometric metal–organic frameworks (nanoMOFs) and further understanding the in vivo effect of the coated material are crucial for the convenient biomedical applications of MOFs. However, in most studies, the surface modification protocol is often associated with significant toxicity and/or lack of selectivity. As an alternative, how the highly selective and general grafting GraftFast method leads, through a green and simple process, to the successful attachment of multifunctional biopolymers (polyethylene glycol (PEG) and hyaluronic acid) on the external surface of nanoMOFs is reported. In particular, effectively PEGylated iron trimesate MIL-100(Fe) nanoparticles (NPs) exhibit suitable grafting stability and superior chemical and colloidal stability in different biofluids, while conserving full porosity and allowing the adsorption of bioactive molecules (cosmetic and antitumor agents). Furthermore, the nature of the MOF–PEG interaction is deeply investigated using high-resolution soft X-ray spectroscopy. Finally, a cell penetration study using the radio-labeled antitumor agent gemcitabine monophosphate (3H-GMP)-loaded MIL-100(Fe)@PEG NPs shows reduced macrophage phagocytosis, confirming a significant in vitro PEG furtiveness.
[hal-01862276] Prevalence and outcome of heparin-induced thrombocytopenia diagnosed under veno-arterial extracorporeal membrane oxygenation a retrospective nationwide study
Date: 3 avr 2021 - 04:24
Desc: Purpose - Thrombocytopenia is a frequent and serious adverse event in patients treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for refractory cardiogenic shock. Similarly to postcardiac surgery patients, heparin-induced thrombocytopenia (HIT) could represent the causative underlying mechanism. However, the epidemiology as well as related mortality regarding HIT and VA-ECMO remains largely unknown. We aimed to define the prevalence and associated 90-day mortality of HIT diagnosed under VA-ECMO. Methods - This retrospective study included patients under VA-ECMO from 20 French centers between 2012 and 2016. Selected patients were hospitalized for more than 3 days with high clinical suspicion of HIT and positive anti-PF4/heparin antibodies. Patients were classified according to results of functional tests as having either Confirmed or Excluded HIT. Results - A total of 5797 patients under VA-ECMO were screened; 39/5797 met the inclusion criteria, with HIT confirmed in 21/5797 patients (0.36% [95% CI] [0.21-0.52]). Fourteen of 39 patients (35.9% [20.8-50.9]) with suspected HIT were ultimately excluded because of negative functional assays. Drug-induced thrombocytopenia tended to be more frequent in Excluded HIT at the time of HIT suspicion (p = 0.073). The platelet course was similar between Confirmed and Excluded HIT (p = 0.65). Mortality rate was 33.3% [13.2-53.5] in Confirmed and 50% [23.8-76.2] in Excluded HIT (p = 0.48). Conclusions - Prevalence of HIT among patients under VA-ECMO is extremely low at 0.36% with an associated mortality rate of 33.3%, which appears to be in the same range as that observed in patients treated with VA-ECMO without HIT. In addition, HIT was ultimately ruled out in one-third of patients with clinical suspicion of HIT and positive anti-PF4/heparin antibodies.
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