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Endothelial Cell Nitric Oxide Synthase (endothelial + cell_nitric_oxide_synthase)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

Reduction expression of thrombomodulin and endothelial cell nitric oxide synthase in dermatomyositis

NEUROPATHOLOGY, Issue 4 2007
Guang-li Shen
Dermatomyositis (DM) is a systemic microvasculitis predominantly involving the capillaries. We investigated the expression of thrombomodulin (TM) and endothelial cell nitric oxide synthase (eNOS) in microvessels of DM patients. Twelve patients with acute or subacute onset of proximal muscle weakness and erythematous rash over their faces and shoulders were included in this study. Serum creatine phosphokinase was elevated in almost all patients. Electromyograph showed a myopathic pattern in all patients. Muscle biopsies were performed in all patients and 10 non-DM controls and studied with histological, enzyme histochemical and immunohistochemical staining. von Willebrand factor, TM and eNOS antibodies were used as the primary antibodies. Perifascicular degeneration and inflammatory cell infiltration in the perimysium were noted in almost all patients. Non-special esterase staining was markedly positive in capillary and microvascular endothelium. Marked reduction in TM and eNOS staining was noted in DM patients in perimysium microvessels and perifascicular area capillaries. Vascular lesions in DM were not only limited to capillaries. The low expression of TM and eNOS in microvessels suggests the anticoagulation and vasodilation functions of vascular endothelium is reduced. DM is an inflammatory vascular endothelial disease. [source]

Hemorheologic profile in systemic sclerosis: Role of NOS3 ,786T>C and 894G>T polymorphisms in modulating both the hemorheologic parameters and the susceptibility to the disease

ARTHRITIS & RHEUMATISM, Issue 7 2006
Cinzia Fatini
Objective Microvascular disorders are relevant in systemic sclerosis (SSc). Hyperviscosity, due to alterations of blood cells and plasma components, may play a role in the pathogenesis of microcirculatory disorders. An impaired availability of nitric oxide, related to polymorphisms in NOS3, the gene for endothelial cell nitric oxide synthase, might influence erythrocyte deformability. We undertook this study to investigate the hemorheologic profile in SSc and the role of NOS3 polymorphisms in modulating the hemorheologic status of SSc patients. Methods We studied 113 consecutive SSc patients (75 with limited cutaneous SSc [lcSSc] and 38 with diffuse cutaneous SSc [dcSSc]) and 113 healthy controls. The hemorheologic profile was obtained by assessing whole blood viscosity (WBV; at shear rates of 0.512 and 94.5 seconds,1), plasma viscosity (PLV; at a shear rate of 94.5 seconds,1), and erythrocyte deformability index (DI). We determined NOS3 polymorphisms by molecular analysis. Results A marked alteration of hemorheologic parameters was found both in patients with lcSSc and in those with dcSSc compared with controls (P < 0.0001). In multivariate analysis, rheologic variables were significantly associated with the disease (for WBV at a shear rate of 94.5 seconds,1, odds ratio [OR] 5.4, 95% confidence interval [95% CI] 1.4,19.9, P = 0.01; for PLV, OR 2.8, 95% CI 1.2,6.5, P = 0.01; for DI, OR 3.9, 95% CI 1.4,10.8, P = 0.007), and NOS3 ,786C and 894T alleles significantly affected the DI (for ,786C allele, OR 2.3, 95% CI 1.01,5.4, P = 0.04; for 894T allele, OR 2.2, 95% CI 1.01,4.8, P = 0.04). The simultaneous presence of the ,786C and 894T alleles represented a susceptibility factor for SSc (OR 2.8, 95% CI 1.4,5.7, P = 0.004). Conclusion Our findings document an altered rheologic profile in SSc and demonstrate a relationship between this alteration and NOS3 polymorphisms, thus shedding light on a potential novel mechanism influencing the microcirculation in this disease. [source]

SICKLE CELL DISEASE: ROLE OF REACTIVE OXYGEN AND NITROGEN METABOLITES

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2007
Katherine C Wood
SUMMARY 1Sickle cell disease (SCD) is an inherited disorder of haemoglobin synthesis that is associated with significant morbidity and mortality due to sequelae of episodic vaso-occlusive events: pain crises and multiorgan damage. The microvascular responses to the initiation, progression and resolution of vaso-occlusive events are consistent with an inflammatory phenotype as suggested by activation of multiple cell types, an oxidatively stressed environment and endothelial cell dysfunction. 2Decreased anti-oxidant defences in SCD patients and mice are accompanied by activation of enzymatic (NADPH oxidase, xanthine oxidase) and non-enzymatic (sickle haemoglobin auto-oxidation) sources of reactive oxygen species. The resultant oxidative stress leads to dysfunction/activation of arteriolar and venular endothelial cells, resulting in impaired vasomotor function and blood cell,endothelial cell adhesion. 3Changes in substrate and cofactor availability for endothelial cell nitric oxide synthase may underlie reactive oxygen- and nitrogen-induced events that contribute to SCD-induced vasculopathy. 4The emerging role of reactive oxygen and nitrogen species in the pathogenesis of SCD provides a platform for the development of novel agents to treat this painful and lethal disease. [source]