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Background Chronic kidney disease (CKD) is associated with increased cardiovascular mortality, frequent vascular calcification (VC) and accumulation of uraemic toxins. Advanced glycation end products and S100 proteins interact with the receptor for advanced glycation end products (RAGE). In the present work, we aimed to investigate the role(s) of RAGE in the CKD–VC process. Methods Apoe−/− or Apoe−/−Ager (RAGE) −/− male mice were assigned to CKD or sham-operated groups. A high-phosphate diet was given to a subgroup of Apoe−/− and Apoe−/−Ager−/− CKD mice. Primary cultures of Ager+/+ and Ager−/− vascular smooth muscle cells (VSMCs) were established and stimulated with either vehicle, inorganic phosphate (Pi) or RAGE ligands (S100A12; 20 µM). Results After 12 weeks of CKD we observed a significant increase in RAGE ligand (AGE and S100 proteins) concentrations in the serum of CKD Apoe−/− mice. Ager messenger RNA (mRNA) levels were 4-fold higher in CKD vessels of Apoe−/ − mice. CKD Apoe−/− but not CKD Apoe−/− or Ager−/− mice displayed a marked increase in the VC surface area. Similar trends were found in the high-phosphate diet condition. mRNA levels of Runx2 significantly increased in the Apoe−/− CKD group. In vitro , stimulation of Ager+/+ VSMCs with Pi or S100A12 induced mineralization and osteoblast transformation, and this was inhibited by phosphonoformic acid (Pi co-transporters inhibitor) and Ager deletion. In vivo and in vitro RAGE was necessary for regulation of the expression of Pit-1, at least in part through production of reactive oxygen species. Conclusion RAGE, through the modulation of Pit-1 expression, is a key molecule in the genesis of VC. [ABSTRACT FROM AUTHOR]

Engineering living, multilayered blood vessels to form in vivo arteries is a promising alternative to peripheral artery bypass using acellular grafts restricted by thrombosis and occlusion at long term. Bone Morphogenetic Protein 2 (BMP2) is a growth factor determining in the early vascular embryonic development. The aim of the present study was evaluate the collaborative effect of recombinant human-BMP2 and Bone marrow-Mesenchymal stem cells (BM-MSCs) seeded on vascular patch to regenerate a vascular arterial wall in a rat model. BM-MSCs expressing green fluorescent protein (GFP) seeded on vascular patch were cultured in presence of recombinant human-BMP2 [100 ng/mL] during 1 week before their implantation on the abdominal aorta of Wistar rats. We observed after 2 weeks under physiological arterial flow a regeneration of a three layers adult-like arterial wall with a middle layer expressing smooth muscle proteins and a border layer expressing endothelial marker. In vitro study, using Matrigel assay and co-culture of BM-MSCs with endothelial cells demonstrated that rh-BMP2 promoted tube-like formation even at long term (90 days) allowing the organization of thick rails. We demonstrated using inhibitors and siRNAs that rh-BMP2 enhanced the expression of HIF-1α and Id1 through, at least in part, the stimulation of JAK2/STAT3/STAT5 signaling pathways. Rh-BMP2 by mimicking embryological conditions allowed vascular BM-MSCs differentiation. [ABSTRACT FROM AUTHOR]

Aims Angiotensin II induces cardiac myocyte apoptosis and hypertrophy, which contribute to heart failure, possibly through enhanced oxidative stress. The aim of this work was to assess the impact of hemin (heme oxygenase-1 inducer) on NADPH oxidase activation, cardiac oxidative stress, and development of fibrosis in a rat model of renovascular hypertensive cardiomyopathy in comparison to an anti-hypertensive reference treatment with losartan. Methods and results A 3week hemin treatment was tested in an angiotensin II-dependent hypertensive rat model and a cellular model of neonatal rat cardiomyocytes stimulated by angiotensin II. Our findings demonstrate that hemin prevented development of intercellular fibrosis, expression of collagen I, and disorganization of intracellular fibres. Oxidative stress and apoptosis evaluated in hypertensive myocardial tissue were decreased by hemin. The reference treatment with the angiotensin II receptor (AT1) antagonist (losartan) was less effective than hemin in prevention of fibrosis and oxidative stress, although it was more effective in reducing hypertension. Rac-1 activation and, subsequently, NADPH oxidase activity were further decreased with hemin than with losartan. Hemin enhanced the expression of phosphoinositide 3-kinase (PI3K) p85 regulatory subunit, in contrast to losartan. The PI3K/Akt signalling pathway activation by hemin was related to heme oxygenase-1 activation and an increase in biliverdin reductase, and its inhibition by LY294002 reversed the effects of hemin on collagen I and caspase-3 expression. Finally, hemin increased Akt activation, and concomitantly decreased RhoA and p38 mitogen-activated protein kinase activation. Conclusion We confirmed a positive effect of hemin on oxidative cardiac damage, apoptosis, and fibrosis induced by hypertension by modulating the NADPH oxidase activation through enhanced expression of the PI3K p85 regulatory subunit. [ABSTRACT FROM AUTHOR]

In this paper, power-sharing management control on an AC islanded microgrid is investigated to achieve accurate reactive power sharing. The droop control method is primarily used to manage the active and reactive power sharing among the DGs in the microgrid. However, the line impedance mismatch causes unbalanced reactive power sharing. As a solution a consensus-based adaptive virtual impedance controller is proposed, where the consensus algorithm is used to set the reactive power mismatch; then a virtual impedance correction term is generated through a proportional-integral controller to eliminate the line impedance mismatch. Thus, reactive power sharing is achieved without knowledge of the line impedances or using a central controller. Moreover, the consensus algorithm is used to restore the AC bus voltage to the nominal value by estimating the DGs average voltage using neighbor communication to compensate for the decreased magnitude of the voltage reference. Matlab/Simulink is used to validate the accuracy of reactive power sharing and voltage restauration achievement of the proposed solution through simulation of different scenarios. In addition, a dSPACE DS1104 is used within a developed experimental testbench based on two parallel DGs to validate the effectiveness of the proposed solution in the real world. [ABSTRACT FROM AUTHOR]

The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor that interacts with advanced glycation end products, but also with C3a, CpG DNA oligonucleotides, and alarmin molecules such as HMGB1 to initiate a proinflammatory reaction. Systemic lupus erythematosus is an autoimmune disorder associated with the accumulation of RAGE ligands. We generated mice invalidated for RAGE in the lupus-prone B6-MRL Fas lpr/j background to determine the role of RAGE in the pathogenesis of systemic lupus erythematosus. We compared the phenotype of these mice with that of their wild-type and B6-MRL Fas lpr/j littermates. Lymphoproliférative syndrome, production of anti-dsDNA Abs, lupus nephritis, and accumulation of CD3+B220+CD4-CD8- autoreactive T cells (in the peripheral blood and the spleen) were significantly increased in B6-MRL Fas lpr/j RAGE-/- mice compared with B6- MRL Fas lpr/j mice (respectively p < 0.005, p < 0.05, p < 0.001, and p < 0.001). A large proportion of autoreactive T cells from B6- MRL Fas lpr/j mice expressed RAGE at their surface. Time course studies of annexin V expression revealed that autoreactive T cells in the spleen of B6-MRL Fas lpr/j-RAGE-/- mice exhibited a delay in apoptosis and expressed significantly less activated caspase 3 (39.5 ±4.3%) than T cells in B6-MRL Fas lpr/j mice (65.5 ± 5,2%) or wild-type mice (75.3 ± 2.64%) (p = 0.02). We conclude that the deletion of RAGE in B6-MRL Fas lpr/j mice promotes the accumulation of autoreactive CD3+B220+CD4-CD8- T cells, therefore exacerbating lymphoproliferative syndrome, autoimmunity, and organ injury. This suggests that RAGE rescues the apoptosis of T lymphocytes when the death receptor Fas/CD95 is dysfunctional. [ABSTRACT FROM AUTHOR]