Microparticles are vectors of paradoxical information in vascular cells including the endothelium: role in health and diseases

Both inflammation and thrombosis can be orchestrated by the interactions between circulating cells, such as leukocytes and platelets, with vascular, endothelial and smooth muscle cells, which, during activation or apoptosis, can release circulating microparticles (MPs). Indeed, MPs are membrane vesicles with procoagulant and proinflammatory properties. MPs are present in blood from healthy individuals and in patients under several pathological states, for instance sepsis, preeclampsia, Crohn\u27s disease and diabetes, strengthening the notion that MPs may play a role in these diseases. Circulating MPs or those generated in vitro from apoptotic T cells display deleterious effects on endothelial and/or vasomotor function. In contrast, MPs might be protective to endothelial cells. We have shown that MPs harboring the morphogen sonic hedgehog may represent a new therapeutic approach against endothelial dysfunction during acute severe endothelial injury. Indeed, these types of MPs induce NO release, decrease production of reactive oxygen species and induce angiogenesis from endothelial cells. This protective role for the endothelium was confirmed also by their in vivo injection in mice in which they were also able to reverse endothelial dysfunction in a model of heart ischemia/reperfusion. On the contrary, MPs from preeclamptic women compared to those from normal pregnant women showed pro-inflammatory properties in the vascular wall inducing vascular hyporeactivity in vessels from humans and mice. These effects were associated with complex interactions between NO and cyclooxygenase systems via endothelial cell activation. Altogether, these findings suggest that MPs can be considered as vectors of biological messages for vascular homeostasis, during immunity and inflammation

Deletion of estrogen receptor-alpha abolishes endothelial response to wine polyphenols without affecting the main cardiovascular parameters in mice

Date du colloque : 10/2009International audienc

PPARδ Activity in Cardiovascular Diseases: A Potential Pharmacological Target

Activation of peroxisome proliferator-activated receptors (PPARs), and particularly of PPARα and PPARγ, using selective agonists, is currently used in the treatment of metabolic diseases such as hypertriglyceridemia and type 2 diabetes mellitus. PPARα and PPARγ anti-inflammatory, antiproliferative and antiangiogenic properties in cardiovascular cells were extensively clarified in a variety of in vitro and in vivo models. In contrast, the role of PPARδ in cardiovascular system is poorly understood. Prostacyclin, the predominant prostanoid released by vascular cells, is a putative endogenous agonist for PPARδ, but only recently PPARδ selective synthetic agonists were found, improving studies about the physiological and pathophysiological roles of PPARδ activation. Recent reports suggest that the PPARδ activation may play a pivotal role to regulate inflammation, apoptosis, and cell proliferation, suggesting that this transcriptional factor could become an interesting pharmacological target to regulate cardiovascular cell apoptosis, proliferation, inflammation, and metabolism

Modelling the Seventies. Image-Based Modelling to Investigate Landscape Change in a Mediterranean Mountain Area

Historical aerial imagery can be used to investigate geomorphological change over time, which can inform research about the preservation and visibility of the archaeological record, as well as heritage management. This paper presents a composite Image-Based Modelling workflow to generate 3D models, historical orthophotos, and historical digital elevation models from images from the 1970s. The main challenge was the lack of high-resolution recent digital elevation models and ground control points. Therefore, spatial data from various sources had to be combined. To assess the accuracy of the final 3D model, the RMSE was calculated. While the workflow appears effective, the low accuracy of the initial data limits the usefulness of the model for the study of geomorphological change. However, it can be implemented to aid sample area selection when preparing archaeological fieldwork, or, when working with different survey datasets, signal areas with a high bias risk resulting from post-depositional processes

Compaction through Buckling in 2D Periodic, Soft and Porous Structures: Effect of Pore Shape

Soft cellular structures that comprise a solid matrix with a square array of holes open avenues for the design of novel soft and foldable structures. Our results demonstrate that by simply changing the shape of the holes the response of porous structure can be easily tuned and soft structures with optimal compaction can be designed.Engineering and Applied Science

Supporting Cross-Organizational Assimilation of IoT Innovation Exemplified by the ChainPORT Initiative

The chainPORT community of port authorities (PAs) around the world gave their commitment to collaborate. Many PAs developed Internet of Things (IoT) based solutions to increase their operational efficiency. Within its IT solutions workgroup, the challenge of supporting the diffusion and assimilation of these IoT innovations was adressed by creating a centralized communication platform for IoT solutions to allow inter-organizational knowledge exchange. We draw upon the knowledge gained by analyzing 24 solutions from 8 port authorities and present concepts on how the specific challenges in this setting were adressed and what principles guided the creation of the emerging IT artifact

Ablation of aquaporin‐9 ameliorates the systemic inflammatory response of lps‐induced endotoxic shock in mouse

Septic shock is the most severe complication of sepsis, being characterized by a systemic inflammatory response following bacterial infection, leading to multiple organ failure and dra-matically high mortality. Aquaporin‐9 (AQP9), a membrane channel protein mainly expressed in hepatocytes and leukocytes, has been recently associated with inflammatory and infectious re-sponses, thus triggering strong interest as a potential target for reducing septic shock‐dependent mortality. Here, we evaluated whether AQP9 contributes to murine systemic inflammation during endotoxic shock. Wild type (Aqp9+/+; WT) and Aqp9 gene knockout (Aqp9−/−; KO) male mice were submitted to endotoxic shock by i.p. injection of lipopolysaccharide (LPS; 40 mg/kg) and the related survival times were followed during 72 h. The electronic paramagnetic resonance and confocal microscopy were employed to analyze the nitric oxide (NO) and superoxide anion (O2−) produc-tion, and the expression of inducible NO‐synthase (iNOS) and cyclooxigenase‐2 (COX‐2), respec-tively, in the liver, kidney, aorta, heart and lung of the mouse specimens. LPS‐treated KO mice survived significantly longer than corresponding WT mice, and 25% of the KO mice fully recov-ered from the endotoxin treatment. The LPS‐injected KO mice showed lower inflammatory NO and O2− productions and reduced iNOS and COX‐2 levels through impaired NF‐κB p65 activation in the liver, kidney, aorta, and heart as compared to the LPS‐treated WT mice. Consistent with these results, the treatment of FaO cells, a rodent hepatoma cell line, with the AQP9 blocker HTS13268 prevented the LPS‐induced increase of inflammatory NO and O2−. A role for AQP9 is suggested in the early acute phase of LPS‐induced endotoxic shock involving NF‐κB signaling. The modulation of AQP9 expression/function may reveal to be useful in developing novel endotoxemia therapeutic