Long Term Stabilization of Expanding Aortic Aneurysms by a Short Course of Cyclosporine A through Transforming Growth Factor-Beta Induction

Abdominal aortic aneurysms (AAAs) expand as a consequence of extracellular matrix destruction, and vascular smooth muscle cell (VSMC) depletion. Transforming growth factor (TGF)-beta 1 overexpression stabilizes expanding AAAs in rat. Cyclosporine A (CsA) promotes tissue accumulation and induces TGF -beta1 and, could thereby exert beneficial effects on AAA remodelling and expansion. In this study, we assessed whether a short administration of CsA could durably stabilize AAAs through TGF-beta induction. We showed that CsA induced TGF-beta1 and decreased MMP-9 expression dose-dependently in fragments of human AAAs in vitro, and in animal models of AAA in vivo. CsA prevented AAA formation at 14 days in the rat elastase (diameter increase: CsA: 131.9±44.2%; vehicle: 225.9±57.0%, P = 0.003) and calcium chloride mouse models (diameters: CsA: 0.72±0.14 mm; vehicle: 1.10±0.11 mm, P = .008), preserved elastic fiber network and VSMC content, and decreased inflammation. A seven day administration of CsA stabilized formed AAAs in rats seven weeks after drug withdrawal (diameter increase: CsA: 14.2±15.1%; vehicle: 45.2±13.7%, P = .017), down-regulated wall inflammation, and increased αSMA-positive cell content. Co-administration of a blocking anti-TGF-beta antibody abrogated CsA impact on inflammation, αSMA-positive cell accumulation and diameter control in expanding AAAs. Our study demonstrates that pharmacological induction of TGF-beta1 by a short course of CsA administration represents a new approach to induce aneurysm stabilization by shifting the degradation/repair balance towards healing

Catheter Injected Bone Marrow Mesenchymal Stem Cells Induce Efficacious Occlusion of Arteriovenous Nidus in a Swine Model

International audienc

Aquatic Walking and Swimming Kinematics of Neonate and Juvenile Epaulette Sharks

The epaulette shark, Hemiscyllium ocellatum, is a small, reef-dwelling, benthic shark that-using its paired fins-can walk, both in and out of water. Within the reef flats, this species experiences short periods of elevated CO2 and hypoxia as well as fluctuating temperatures as reef flats become isolated with the outgoing tide. Past studies have shown that this species is robust (i.e., respiratory and metabolic performance, behavior) to climate change-relevant elevated CO2 levels as well as hypoxia and anoxia tolerant. However, epaulette shark embryos reared under ocean warming conditions hatch earlier and smaller, with altered patterns and coloration, and with higher metabolic costs than their current-day counterparts. Findings to date suggest that this species has adaptations to tolerate some, but perhaps not all, of the challenging conditions predicted for the 21st century. As such, the epaulette shark is emerging as a model system to understand vertebrate physiology in changing oceans. Yet, few studies have investigated the kinematics of walking and swimming, which may be vital to their biological fitness, considering their habitat and propensity for challenging environmental conditions. Given that neonates retain embryonic nutrition via an internalized yolk sac, resulting in a bulbous abdomen, while juveniles actively forage for worms, crustaceans, and small fishes, we hypothesized that difference in body shape over early ontogeny would affect locomotor performance. To test this, we examined neonate and juvenile locomotor kinematics during the three aquatic gaits they utilize-slow-to-medium walking, fast walking, and swimming-using 13 anatomical landmarks along the fins, girdles, and body midline. We found that differences in body shape did not alter kinematics between neonates and juveniles. Overall velocity, fin rotation, axial bending, and tail beat frequency and amplitude were consistent between early life stages. Data suggest that the locomotor kinematics are maintained between neonate and juvenile epaulette sharks, even as their feeding strategy changes. Studying epaulette shark locomotion allows us to understand this-and perhaps related-species' ability to move within and away from challenging conditions in their habitats. Such locomotor traits may not only be key to survival, in general, as a small, benthic mesopredator (i.e., movements required to maneuver into small reef crevices to avoid aerial and aquatic predators), but also be related to their sustained physiological performance under challenging environmental conditions, including those associated with climate change-a topic worthy of future investigation

Endovascular Cell Therapy Introducing an Anatomical Sparing Strategy in a Preclinical Model of Aortic Isthmus Saccular Aneurysm

International audienceNo abstract availabl

Heterogeneity in the remodeling of aneurysms of the ascending aorta with tricuspid aortic valves.

OBJECTIVES: The study addresses mechanisms driving the formation of ascending aortic aneurysms by comparing the maximal dilatation area with the transition area immediately adjacent to the normal aortic tissue left in place during surgical repair. METHODS: Aortic wall specimens were taken from the maximal dilatation area and transition area in 10 patients undergoing surgery for ascending aortic aneurysms and fixed for histology and immunohistochemistry for vascular smooth muscle cells (alpha-actin), endothelial cells (CD31), and macrophages (CD68). Tissue concentrations of vascular endothelial growth factor, matrix metalloproteinase-2, and matrix metalloproteinase-9 were determined by enzyme-linked immunosorbent assay. The results are expressed as medians with their 25th and 75th centiles. RESULTS: Vascular smooth muscle cells were significantly more abundant in the maximal dilatation area than in the transition area (20.3 [14.8-24.4]/10(-2) mm2 vs 8.0 [6.4-9.3]/10(-2) mm2, respectively, P = .002). In the maximal dilatation area, vascular smooth muscle cells had lost their typical lamellar organization, whereas it was preserved in the transition area. Microvessels were significantly more abundant in the media of transition area than in the maximal dilatation area (7.5 [2.9-10.1]/mm2 vs 1.75 [1.5-2.0]/mm2, respectively, P = .008) and were associated with an inflammatory cell infiltration that predominated in their immediate vicinity. There were no significant differences in vascular endothelial growth factor, matrix metalloproteinase-2, and matrix metalloproteinase-9 between both areas. CONCLUSIONS: The transition area appears as a disease progression front characterized by microvessel formation and inflammatory cell infiltration. In contrast, increased vascular smooth muscle cell density in the maximal dilatation area suggests a healing process, although inefficient to prevent aortic dilatation

Localisation forcée en ville : injustices spatiales et politiques de déguerpissement

Nous souhaitons questionner les notions de justice et d'injustice spatiale en étudiant les déplacements forcés de citadins, nous les désignerons sous le terme, utilisé en Afrique de l'Ouest francophone, de « déguerpissements ». Nous analysons des déguerpissements actuels et passés dans l'optique d'interroger différentes échelles de temps. Communs à de nombreuses villes du Sud, les déguerpissements sont décidés par des autorités étatiques ou municipales et/ou des investisseurs privés, en raison de la valeur symbolique et marchande de certains lieux notamment centraux (dans quatre villes caractérisées par une forte croissance spatiale et démographique). Ces déguerpissements concernent des catégories de citadins vulnérables car considérés « indésirables » (étrangers, minorités, déplacés de guerre, pauvres, etc.). L'objectif est ici de traiter de localisation injuste et du traitement inégal de certains groupes territorialisés, rejoignant l'idée d'Edward Soja : « les discriminations liées aux localisations (discriminations localisationnelles), résultat du traitement inégal fait à certaines catégories de population en raison de leur localisation géographique, s'avèrent fondamentales dans la production d'injustice spatiale et dans la production de structures spatiales pérennes, fondées sur privilèges et avantages. » (Soja, 2009) Nous proposons ainsi d'interroger les injustices spatiales produites par les rapports de force encadrant chaque déguerpissement en envisageant les processus dans la durée : le temps précédant le déguerpissement, accompagné de possibles négociations, le moment de la prise de décision et des éventuelles compensations, et le temps suivant le déguerpissement, de la relocalisation. Ces différents temps, imbriqués les uns dans les autres, interrogent diverses dimensions des injustices dans le processus de territorialisation/déterritorialisation des citadins déguerpis. Pour cerner les différentes formes d'injustices, nous partirons des discours produits par les acteurs qui mettent en place les déguerpissements pour nous interroger par la suite sur les sentiments d'injustice des citadins visés par les politiques. Le sentiment d'injustice est-il lié à la procédure en elle-même du déplacement, aux conditions de départ, aux caractéristiques de l'espace de réinstallation ou au fait d'être relégués dans des espaces éloignés du centre-ville ? Comment les relations de pouvoir entre acteurs nous permettent-elles de saisir la production d'un rapport injuste à l'espace urbain ? Des discours, des logiques légitiment les déguerpissements au nom d'une remise en ordre (les quartiers déguerpis sont généralement considérés comme « sales », « insalubres », « surpeuplés », etc.) et d'une mise en compétition des espaces urbains (mettre en valeur les espaces centraux des grandes villes)

Localisation forcée en ville: injustice spatiale et politique de déguerpissements

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