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%0 Thesis
%A Grau, Marijke
%T Relevanz der enzymatischen NO-Synthese im Erythrozyten: Protektion gegen reaktive Sauerstoffspezies
%C Aachen
%I Publikationsserver der RWTH Aachen University
%M RWTH-CONV-114004
%P 136 Bl. : graph. Darst.
%D 2010
%Z Aachen, Techn. Hochsch., Diss., 2010
%X The red blood cell nitric oxide synthase (RBC-NOS) is against general belief not only an inactive enzyme but produces NO• through the conversion of L-arginine to L-citrulline which is involved in the regulation of platelet aggregation. The RBC-NOS therefore represents an intracellular source for NO• whose importance is not completely understood by now. A comparative clinical trial, comparing young healthy volunteers with subjects showing a cardiovascular risk profile and patients with cardiovascular disease (coronary artery disease and type II diabetes), revealed that cardiovascular disease is associated with limited NO•-production and deteriorated rheologic properties in red blood cells. Based on these findings this work showed that RBC-NOS generated NO• plays a pivotal role in the regulation of red blood cell aggregation and deformability. It also represents an effective defence mechanism against the damaging impact of reactive oxygen species. NO• deficiency within red blood cells through inhibition of RBC-NOS in conclusion leads to decreased deformability and increased aggregation. Moreover, the inhibition induces the uncoupling of the enzyme and enhances the generation of reactive oxygen species. Limited NO• production in combination with extracellular and intracellular enhanced oxidative stress amplifies the negative influence on the hemorheologic properties leading to almost complete rigidity and quicker formation of red blood cell aggregates. Patients with cardiovascular disease do not show reduced RBC-NOS mRNA gene expression levels. A limited NO•-synthesis and impaired rheologic properties are instead caused by a declined RBC-NOS activity. Elevated LDL and triglyceride concentrations in combination with the presented results lead to the conclusion that the RBC-NOS is uncoupled in patients with cardiovascular disease. The present work provides important insights into the function of red blood cell derived NO• which is more than a regulator of hemorheology but is of essential importance when it comes to pathophysiological conditions. These results may help to develop approaches for early diagnosis and therapy to improve the circulatory properties of red blood cells in patients with type II diabetes, coronary artery disease and atherosclerosis through a substrate independent increase of RBC-NOS activity.
%K Erythrozyt (SWD)
%K Stickstoffmonoxid (SWD)
%K Stickstoffmonoxid-Synthase (SWD)
%K Oxidativer Stress (SWD)
%F PUB:(DE-HGF)11
%9 Dissertation / PhD Thesis
%U https://publications.rwth-aachen.de/record/51744