Connexin37 reduces smooth muscle cell proliferation and intimal hyperplasia in a mouse model of carotid artery ligation.

Intimal hyperplasia (IH) is an abnormal response to vessel injury characterized by the dedifferentiation, migration, and proliferation of quiescent vascular smooth muscle cells (VSMC) to form a neointima layer. Vascular connexins (Cx) are involved in the pathophysiology of various vascular diseases, and Cx43, the main Cx expressed in VSMC, has been shown to promote VSMC proliferation and IH. The aim of this study was to investigate the participation of another Cx, namely Cx37, in the formation of the neointima layer. Wild-type (WT) and Cx37-deficient (Cx37-/-) C57BL/6J mice were subjected to carotid artery ligation (CAL), a model of vessel injury and IH. The neointima developed linearly in WT until 28 days post surgery. In contrast, the neointima layer was almost absent 14 days after surgery in Cx37-/- mice, and twice as more developed after 28 days compared to WT mice. This large neointima formation correlated with a two-fold increase in cell proliferation in the media and neointima regions between 14 and 28 days in Cx37-/- mice compared to WT mice. The CAL triggered Cx43 overexpression in the media and neointima layers of ligated carotids in WT mice, and selectively up-regulated Cx37 expression in the media layer, but not in the neointima layer. The de novo expression of Cx37 in human primary VSMC reduced cell proliferation and P-Akt levels, in association with lower Cx43 levels, whereas Cx43 overexpression increased P-Akt levels. The presence of Cx37 in the media layer of injured arteries restrains VSMC proliferation and limits the development of IH, presumably by interfering with the pro-proliferative effect of Cx43 and the Akt pathway

Modeling Cl- concentration and 37 Cl profiles in porewater across a 250m-thick inducated argillite at the Tournemire URL (France)

International audienceDissolved chloride in argillite porewater has been studied as a natural analogue for radionuclides potentially released from radioactive waste disposal. The Tournemire URL intersects impervious and compacted argillite. A previously obtained chloride concentration profile of intact rock is symmetric with a maximum concentration of 0.6±0.1 g/L, compared to 19 g/L for the original connate seawater. Dissolved chloride shows high δ37Cl values, ranging between +6 and +8‰ vs. SMOC. The modeled profile considers diffusive exchange between connate seawater and meteoric freshwater. Transport parameters were obtained by radial diffusion experiments. Numerical modeling was performed with the coupled reactive-transport code Hytec. Simulations suggest a diffusive-exchange time of 85±10 Ma for Cl, which correlates with a major erosional period. Simulated δ37Cl values between 1.002 and agree with observed porewater δ37Cl. This study strongly suggests that the dissolved chloride profile in the argillites results from diffusive exchange and indicates that unfractured argillites can provide good confinement

Hydro(geo)logical and geochemical approach to investigate the impact of active layer groundwater on runoff in the Austrelovenbreen watershed (Western Spitsbergen - 79°N)

International audienc

Chlorine transport processes through a 2000 m aquifer/aquitard system

International audienceIn the Paris Basin, in France, the Callovo-Oxfordian (COx) is currently studied over a 250 km2 surface area by the French national radioactive waste management agency in order to assess the feasibility of long-term underground nuclear waste repository. The COx is a 140 m thick clay-rich layer, which is part of the 2000 m aquitard/aquifer system constituting the sedimentary cover. In such sedimentary context, the transport processes of potential contaminants can be represented by both vertical diffusion and horizontal advection through the most permeable layers. Chloride is used as a natural conservative tracer, and is monitored in term of concentrations and isotopic composition (δ37Cl) for both pore and groundwater. During this study, the samples were collected from three boreholes located in the center of the studied zone, one of them (EST433) going down to 2000 m depth. The main solute transport process is shown to be vertical diffusion from the massive Keuper halite level to the rest of the sedimentary pile. This global diffusive system can be occasionally disturbed by horizontal circulation of groundwater occurring in the Oxfordian and Dogger limestone formations. Therefore, these circulations cut the global diffusive system in a succession of independent diffusive systems. In this study the data set was implemented in a simplified 2D solute transport model and scenarii reproducing known history in term of paleo circulations inside the system, were applied and allowed to obtained a good fit of the data. Model results showed that paleo circulations, occurring between −145 Ma and −110 Ma, still have an impact on current distribution of chloride in the system, especially for δ37Cl. The model highlights the need of the presence of a circulation spatially limited at the base of the Liassic formation to fit the data. The best fit obtained indicated current residence time of 500 ka in the Dogger and Oxfordian, with respective onset of the circulations at −20 Ma and −5 Ma

Relationship between type of unprovoked venous thromboembolism and cancer location: An individual patient data meta-analysis

International audienc