Endothelial cell dysfunction (ECD) is emerging as the common denominator for diverse and highly prevalent cardiovascular diseases. Recently, an increased number of procoagulant circulating endothelial microparticles (EMPs) has been identified in patients with acute myocardial ischemia, preeclampsia, diabetes, which suggests that these particles represent a surrogate marker ECD. Our previous studies showed potential mobilization by PAI-1. The aim this study was to test effects isolated EMPs...

Generation of reactive oxygen species and nitric oxide in hypoxia-reperfusion injury may form a cytotoxic metabolite, peroxynitrite, which is capable causing lipid peroxidation DNA damage. This study was designed to examine the contribution oxidative nitrosative stress renal damage ischemic acute failure (iARF). iARF initiated rats by 45-min artery clamping. resulted peroxidation, damage, nitrotyrosine modification confirmed both Western immunohistochemical analyses. Three groups animals...

There is accumulating circumstantial evidence suggesting that endothelial cell dysfunction contributes to the “no-reflow” phenomenon in postischemic kidneys. Here, we demonstrated vulnerability of vitro, ex vivo, and vivo cells exposed pathophysiologically relevant insults, such as oxidative nitrosative stress or ischemia. All these stimuli compromised integrity lining. Next, performed minimally invasive intravital microscopy blood flow peritubular capillaries, which provided direct...

Hyperhomocysteinemia (HHCy) is an independent and graded cardiovascular risk factor. HHCy prevalent in patients with chronic renal failure, contributing to the increased mortality rate. Controversy exists as effects of on nitric oxide (NO) production: it has been shown that both increases suppresses it. We addressed this problem by using amperometric electrochemical NO detection a porphyrinic microelectrode study responses endothelial cells incubated homocysteine (Hcy) stimulation...

First Published July 12, 2001; 10.1152/ajprenal.0071.2001.—Generation of reactive oxygen species and nitric oxide in hypoxia-reperfusion injury may form a cytotoxic metabolite, peroxynitrite, which is capable causing lipid peroxidation DNA damage. This study was designed to examine the contribution oxidative nitrosative stress renal damage ischemic acute failure (iARF). iARF initiated rats by 45-min artery clamping. resulted peroxidation, damage, nitrotyrosine modification confirmed both...

Although the accelerated atherosclerosis and premature aging of cardiovascular system in patients with metabolic syndrome have been appreciated, mechanisms their development potential therapeutic interventions remain unresolved. Our previous studies implicated advanced glycosylation end products senescence preventable a peroxynitrite scavenger, ebselen. Therefore, effect ebselen on endothelial vasculopathy model syndrome--Zucker diabetic rats (ZDF)--was investigated. Ebselen decreased...

Endothelium-derived microparticles have recently been described as a new marker of endothelial cell dysfunction. Increased levels circulating documented in inflammatory disorders, diabetes mellitus, and many cardiovascular diseases. Perturbations angiogenesis play an important role the pathogenesis these disorders. We demonstrated previously that isolated (EMPs) impair function vitro, diminishing acetylcholine-induced vasorelaxation nitric oxide production by rat aortic rings simultaneously...

The recent refinement and computerization of intravital microscopy have permitted us to monitor microcirculation in vivo with minimal invasion. Here, we report on the first findings made use a pencil-lens microscope as applied ischemic rat kidney. Peritubular capillary glomerular blood flow were monitored under basal conditions, during renal artery occlusion, immediately after release clamp. Erythrocyte velocity was calculated an angle consecutive spatiotemporal images. Intravital...

Excessive anticoagulation with warfarin can result in acute kidney injury (AKI) by causing glomerular hemorrhage and renal tubular obstruction red blood cell (RBC) casts some patients, especially those chronic disease (CKD). This condition was described as warfarin-related nephropathy (WRN). Recent evidence suggests that WRN-like syndromes are not confined to warfarin, but may be seen other anticoagulants, such dabigatran. The aim of this study investigate dabigatran effects on function an...

ABSTRACT. Zucker diabetic fat (ZDF) rats with the metabolic syndrome and hyperlipidemia develop focal segmental sclerosis. The role of oxidative nitrosative stress in nephropathy ZDF was studied. Renal histology, function, immunohistologic biochemical parameters were evaluated at 8 22 wk age lean (ZL) after chronic treatment ebselen, an antioxidant peroxinitrite scavenger. At wk, showed hyperglycemia, no proteinuria or nephropathy, but higher levels dihydrobiopterin 3-nitrotyrosine...

Nitric oxide (NO) derived from endothelial cells is profoundly related to the maintenance of physiological vascular tone. Impairment NO generation brought about by gene polymorphism considered major deterioration factor for progressive renal disease, including diabetic nephropathy. The present study aimed elucidate Glu298Asp synthase (eNOS) in patients with end-stage disease (ESRD) and its role as a predisposing cardiovascular complications. exon 7 eNOS was determined polymerase chain...

Diabetic vasculopathy is central to the development of diverse cardiovascular, renal, retinal, and neurological complications diabetes. We previously demonstrated that growth endothelial cells on glycated extracellular matrix proteins (collagen matrigel) results in a significant decrease cell proliferation. In present study, we show early-passage human umbilical vein (HUVECs) grown collagen (GC) express hallmarks premature senescence, ie, increase proportion expressing senescence-associated...

Endothelial dysfunction is emerging as a common denominator for diverse and highly prevalent cardiovascular diseases. Increased level of plasminogen activator inhibitor-1 (PAI-1) procoagulant activity have been recognized hallmarks endothelial dysfunction. This study was aimed at investigating cellular actions PAI-1 potential link between state.Human umbilical vein cells treated with were subjected to laser confocal fluorescence microscopy, immunoprecipitation Western blotting, FACS analysis...

Endothelial dysfunction accompanies suboptimal glucose control in patients with diabetes mellitus. A hallmark of endothelial is a deficiency production or bioavailability vascular nitric oxide (NO). Here we demonstrate that acute exposure human cells to glucose, at levels found plasma diabetic patients, results significant blunting NO responses the synthase (eNOS) agonists bradykinin and A-23187. Monitoring generation by purified recombinant bovine eNOS vitro, using amperometric...