Summary Vascular endothelial dysfunction occurs during the human aging process, and it is considered as a crucial event in development of many vasculopathies. We investigated underlying mechanisms this particularly those related with oxidative stress inflammation, vasculature subjects aged 18–91 years without cardiovascular disease or risk factors. In isolated mesenteric microvessels from these subjects, an age‐dependent impairment endothelium‐dependent relaxations to bradykinin was...

Activation of Janus kinase/signal transducers and activators transcription (JAK/STAT) is an important mechanism by which hyperglycemia contributes to renal damage, suggesting that modulation this pathway may prevent vascular complications diabetes. Here, we investigated the involvement suppressors cytokine signaling (SOCS) as intracellular negative regulators JAK/STAT activation in diabetic nephropathy. In a rat model, inducing diabetes resulted increased expression SOCS1 SOCS3. humans,...

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a prevalent clinical condition associated with elevated morbidity and mortality rates. Patients MASLD treated semaglutide, glucagon-like peptide-1 receptor agonist, demonstrate improvement in terms of damage. However, the mechanisms underlaying this beneficial effect are not yet fully elucidated. We investigated efficacy semaglutide halting progression using genetic mouse model diabesity. Leptin-receptor-deficient mice...

Abstract The mechanisms of glomerular damage in IgA nephropathy remain undefined. Mesangial cells (MC) possess Fc receptors for (Fc alpha R), and their occupancy triggers cytokine expression, cell proliferation, extracellular matrix synthesis. In cultured human MC we examined the effects soluble aggregates (AIgA) on activation nuclear factor-kappa B (NF-kappa B) production proinflammatory chemokines monocyte chemoattractant protein-1 (MCP-1), IL-8, IFN-inducible protein-10 (IP-10). exposure...

IgA nephropathy, a primary glomerulonephritis, is principally characterized by mesangial deposits of immune complexes. Recently, it has been demonstrated that cultured glomerular cells (MC) express Fc alpha and gamma receptors. In this work, we studied whether the interaction soluble aggregates IgG (AIgA AIgG) with MC triggers number responses, including generation release inflammatory mediators, cell proliferation, catabolism Aggregates bound to were catabolized in time-dependent manner....

Suppressors of cytokine signaling (SOCS) proteins are intracellular regulators receptor signal transduction, mainly Janus kinase/signal transducers and activators transcription (JAK/STAT). We investigated the effects SOCS modulation on JAK/STAT-dependent responses in vascular cells, their implication atherosclerotic plaque development.Immunohistochemistry human plaques revealed a high expression SOCS1 SOCS3 by smooth muscle cells (VSMCs) macrophages inflammatory region shoulders, when...

Heat shock proteins (HSPs) are induced by cellular stress and function as molecular chaperones that regulate protein folding. Diabetes impairs the function/expression of many HSPs, including HSP70 HSP90, key regulators pathological mechanisms involved in diabetes complications. Therefore, we investigated whether pharmacological HSP90 inhibition ameliorates diabetes-associated renal damage atheroprogression a mouse model combined hyperglycemia hyperlipidemia (streptozotocin-induced diabetic...

Interactive relationships between metabolism, inflammation, oxidative stress, and autophagy in the vascular system play a key role pathogenesis of diabetic cardiovascular disease. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is stress-sensitive guarantor cellular homeostasis, which cytoprotective contributions extend beyond antioxidant defense. We investigated beneficial effects underlying mechanisms Nrf2 inducer tert-butyl hydroquinone (tBHQ) on diabetes-driven atherosclerosis. In...

Abstract. Fas ligand (FasL) is a cell membrane cytokine that can promote apoptosis through activation of receptors. receptor induces glomerular in vivo and participates tubular death during acute renal failure. However, there little information on the expression FasL kidney. This study reports mRNA protein are present normal mouse rat In situ hybridization immunohistochemistry showed proximal epithelium main site addition, increased total kidney de novo by cells were observed two different...

IgG Fc receptors (FcγRs) play a role in activating the immune system and maintaining peripheral tolerance, but their atherosclerosis is unknown. We generated double-knockout (DKO) mice by crossing apolipoprotein E–deficient (apoE −/− ) with FcγR γ chain–deficient (γ ). The size of atherosclerotic lesions along aorta was approximately 50% lower DKO compared apoE control mice, without differences serum lipid levels. macrophage T-cell content were reduced 49±6% 56±8%, respectively, lesions....

Objective— Activation of transcription factor NF-κB is an important step in the development vascular damage, because it controls inducible genes, including many inflammatory mediators. The pharmacological modulation this process main objective design new therapies for atherosclerosis. In work we analyzed effects natural compound parthenolide (PTN), inhibitor. Methods and Results— smooth muscle cells (VSMCs) monocytes stimulated with lipopolysaccharide (LPS), nontoxic doses PTN reduced IκBα...

Abstract Previous works have demonstrated that mesangial cells (MC) possess Fc receptors for IgG. We investigated whether serum IgA could bind to MC in culture through a specific receptor. The binding of 125I-IgA (4 degrees C, 60 min) was dose dependent and saturable, the Scatchard analysis revealed population 1 x 10(5) sites per cell with Ka 7.8 10(8) M-1. This receptor because unlabeled its fragment were able inhibit binding, whereas IgG, IgM, F(ab) not. Parallel experiments showed human...

Reactive oxygen species (ROS) participate in atherogenesis through different mechanisms including oxidative stress and inflammation. Proteins implicated both processes, such as mitogen-activated protein kinase (MEK) some NADPH oxidase (NOX) subunits, are heat shock protein-90 (HSP90) client proteins. In this work, we investigated the antioxidant properties of HSP90 inhibitor, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) experimental atherosclerosis.Treatment ApoE(-/-) mice...

Activation of Janus kinase/signal transducers and activators transcription (STAT) pathway by hyperglycemia dislypidemia contributes to the progression diabetic complications, including atherosclerosis. Suppressor cytokine signaling (SOCS) proteins negatively regulate kinase/STAT have emerged as promising target for anti-inflammatory therapies. We investigated whether a cell-permeable lipopeptide corresponding kinase inhibitory region SOCS1 could reduce atherosclerosis in mice identified...

Background Klotho is a renal protein with anti-aging properties that downregulated in conditions related to kidney injury. Hyperlipidemia accelerates the progression of damage, but mechanisms deleterious effects hyperlipidemia remain unclear. Methods We evaluated whether modulates expression kidneys from C57BL/6 and hyperlipidemic apolipoprotein E knockout (ApoE KO) mice fed normal chow diet (ND) or Western-type high cholesterol-fat (HC) for 5 10 weeks, respectively. Results In ApoE KO mice,...