Reducing the impact of modern industrial production on the environment and reducing the waste generated is undoubtedly one of the most discussed topics of the present time. In the production of fossil-fueled electricity, a large amount of fine-grained waste fly ash is generated. The possible use of ash as secondary raw materials in the construction and building materials industry is one of the many environmental challenges that the energy industry is concerned with. The aim of this diploma thesis was to verify possibilities of utilization of different kinds of power station fly ash as filler in asphalt mixtures for the production of oxidized asphalt insulation strips. The main emphasis was put on the clarification of the influence of the properties of the different types of fly ashes on the resulting rheological behavior of the mixture of asphalt binder and power fly ash, which is professionally called mastic. Mastic forms a technology-critical insulating layer in the asphalt insulation strip. The prediction of the rheological properties and therefore the workability of mastic appears to be an essential element in the management of production, especially under the conditions of the variability of input raw materials. In order to solve the assigned task it was necessary to perform detailed analyzes of fly ash properties, to select the corresponding quantification variable for assessment of the mastic processability and to find the signal fly ash properties, which appears to be a control parameter of workability. As a suitable method for assessing the processability of mastic, a shear viscosity measurement method was chosen. On the basis of the findings, it is possible to state that the use of fly ash from the production of oxidized asphalt bands is not recommended as the mastic prepared from these fly ashes are unprocessed at the assumed concentrations. The negative effect of fly ash after denitrification on the mastic processability has not been demonstrated.

No description available.

Lipids are a structurally diverse class of biomolecules which can undergo a variety of chemical modifications. Among them, lipid (per)oxidation attracts most of the attention due to its significance in the regulation of inflammation, cell proliferation and death programs. Despite their apparent regulatory significance, the molecular repertoire of oxidized lipids remains largely elusive as accurate annotation of lipid modifications is complicated by their low abundance and often unknown, biological context-dependent structural diversity. Here, we provide a workflowbased on the combination of bioinformatics and LC-MS/MS technologies to support identification and relative quantification of oxidized complex lipids in a modification type- and position-specific manner. The developed methodology is used to identify epilipidomics signatures of lean and obese individualswith and without type 2 diabetes. The characteristic signature of lipid modifications in lean individuals, dominated by the presence of modified octadecanoid acyl chains in phospho- and neutral lipids, is drastically shifted towards lipid peroxidation-driven accumulation of oxidized eicosanoids, suggesting significant alteration of endocrine signalling by oxidized lipids in metabolic disorders.

[pt] Nas últimas décadas, a procura por petróleo e gás aumentou, levando à identificação de novos campos petrolíferos em ambientes de reservatórios desafiadores, caracterizados por condições de alta pressão e alta temperatura (HPHT). O desenvolvimento de fluidos de perfuração de base aquosa de alto desempenho com propriedades personalizadas visa aprimorar os processos de extração na indústria petrolífera e reduzir a contaminação ambiental causada principalmente por fluidos à base de óleo. Este estudo tem como objetivo investigar como variações em parâmetros como temperatura, pressão e concentração impactam nas propriedades térmicas e reológicas de suspensões de goma xantana com nanoestruturas de nitreto de boro hexagonal oxidado (hBN-oxi). A condutividade térmica foi significativamente aumentada pela adição de nanopartículas de hBN-oxi (suspensão de 6,0 por cento em peso) ao fluido base, atingindo um aumento de até 12 por cento a 70 graus C. Estas nanoestruturas desempenharam um papel crucial na preservação da condutividade térmica das suspensões de goma xantana, mesmo em temperaturas elevadas. A suspensão com concentração mais alta apresentou tensão limite de escoamento e quando submetida a altas taxas de cisalhamento, sofreu uma queda de viscosidade de apenas 16 por cento a 80 graus C. Estes efeitos adversos da temperatura e pressão sobre a viscosidade foram mitigados pela interação entre a matriz polimérica e o hBN-oxi. No geral, o estudo destacou o potencial do nitreto de boro como nanoaditivo para fluidos de perfuração convencionais, mostrando que formulações adequadamente projetadas podem melhorar o desempenho mesmo em condições desafiadoras sem causar danos ao meio ambiente, graças à alta estabilidade térmica e química do material. / [en] In recent decades, the demand for oil and gas has surged, prompting the identification of new oil fields in challenging reservoir environments those characterized by high-pressure and high-temperature (HPHT) conditions. The development of high-performance aqueous-based drilling fluids with tailored properties aims to enhance extraction processes in the oil industry and reducing environmental contamination mainly caused by oil-based fluids. This study aims to investigate how variations in parameters such as temperature, pressure and concentration impact the thermal and rheological properties of xanthan gum suspensions with oxidized hexagonal boron nitride (hBN-oxi) nanostructures. The thermal conductivity was significantly increased by the addition of hBN-oxi nanoparticles (6.0 wt percent suspension) to the base fluid, reaching an increase of up to 12 percent at 70 degrees C. These nanostructures played a crucial role in preserving the thermal conductivity of xanthan gum suspensions even at elevated temperatures. The presence of nanoparticles at the highest concentration induced a yield stress in the fluid and when subjected to high shear rates, experienced a viscosity drop of only 16 percent at 80 degrees C. These adverse effects of temperature and pressure on viscosity were mitigated by the interaction between the polymer matrix and hBN-oxi. Overall, the study highlighted the potential of boron nitride as a nanoadditive for conventional drilling fluids, showing that properly designed formulations can improve performance even in challenging conditions without causing harm to the environment, thanks to the material s high thermal and chemical stability.

For peanuts, roasted at 170 °C, the formation of selected glycerol-bound oxidized fatty acids (GOFAs), namely 9-oxononanoic acid (9-ONA), azelaic acid (AZA) and octanoic acid, was observed by GC-MS (EI). The content of octanoic acid as well as AZA increased with continuous roasting time (from 59 mg/kg peanut oil to 101 mg/kg peanut oil and from not detectable to 8 mg/kg peanut oil, respectively), whereas the content of 9-ONA initially decreased from 25 mg/kg peanut oil to 8 mg/kg peanut oil (20 min) and increased again up to 37 mg/kg peanut oil following roasting for 40 min. Due to its aldehyde function, 9-ONA could contribute to amino acid side chain modifications as a result of lipation, which could directly influence the functional properties of peanut proteins. Both 9-ONA and octanoic acid are potential markers of thermal processes. Furthermore, in model experiments using methyl linoleate and methyl oleate, up to 18 oxidized fatty acids could be identified as methyl esters, 9-ONA as well as octanoic acid as major components and a faster formation of GOFAs under roasting conditions (170 °C, 20 min). In addition, 9-ONA contributes to the formation of AZA and octanoic acid in both free and bound form as a result of oxidative subsequent reactions in presence of iron (III).

Le CD36 est un récepteur éboueur de classe B exprimé par plusieurs types cellulaires dont les macrophages et les cellules endothéliales de la microvasculature. Le CD36 présente une haute affinité de liaison pour les ligands lipidiques tels que les lipoprotéines oxydées de basse densité (LDLox). De part sa capacité à internaliser les LDLox au niveau des macrophages et de son implication dans la formation des cellules spumeuses, le CD36 joue un rôle critique dans le développement des lésions athérosclérotiques. Nous avons testé l'hypothèse selon laquelle le EP 80317, un ligand synthétique sélectif du CD36, exerce des effets anti-athérosclérotiques chez les souris déficientes en apolipoprotéine E. Un traitement prolongé (12 semaines) avec le EP 80317 réduit fortement (de 51%) la surface des lésions athérosclérotiques par comparaison aux souris témoins. L'effet anti-athérosclérotique est associé à une diminution des taux de cholestérol plasmatique, à une réduction de l’internalisation des LDLox au niveau des macrophages et à une augmentation de l’expression des protéines impliquées dans le transport inverse du cholestérol. De plus, un traitement par le EP 80317 est également associé une diminution de l’expression aortique et plasmatique de protéines pro-inflammatoires. Nos études ont aussi montré un rôle pour le CD36 dans le recrutement des phagocytes mononucléés au niveau des lésions athérosclérotiques, tel que démontré par une réduction de l’accumulation des phagocytes mononucléés radiomarqués CD36–/– par rapport aux cellules CD36+/+. À l’échelle moléculaire, nous avons montré que les phospholipides oxydés induisent la phosphorylation de la kinase Pyk2 des podosomes des monocytes/macrophages de manière dépendante de l’expression du CD36 et de Src. Cette phosphorylation est atténuée par un traitement par le EP80317. Nos résultats appuient le rôle important du CD36 dans l’athérosclérose et suggèrent que les ligands synthétiques qui modulent la fonction du CD36 représentent potentiellement une nouvelle classe d'agents anti-athérosclérotiques. Le CD36 exprimé par les cellules endothéliales de la microvasculature est un récepteur de l’hétérodimère protéique S100A8/A9. Ces protéines s’associent à l’acide arachidonique intracellulaire (AA) des neutrophiles polymorphonucléaires (PMN) et le complexe S100A8/A9/AA peut être sécrété par les PMN activés au contact de l’endothélium. Nous avons vérifié l’hypothèse selon laquelle le CD36 exprimé par la microvasculature est impliqué dans le métabolisme transcellulaire de l’AA par la liaison du complexe S100A8/A9/AA et la réponse inflammatoire. Chez deux modèles murins d'inflammation aiguë (ischémie/reperfusion des membres inférieurs et poche d’air dorsale), nous avons observé que la réponse inflammatoire, notamment l’accumulation des PMN au niveau des sites inflammatoires, est diminuée en moyenne de 63% chez les souris CD36-/-. De même, un traitement par le EP 80317 ou par les anticorps anti-S100A8/A9 diminue chacun de 60% en moyenne l’extravasation des PMN vers les tissus inflammatoires. L’administration simultanée des deux traitements n’a aucun effet supplémentaire, et ces traitements n’exercent aucun effet chez les souris CD36-/-. Nos résultats appuient le rôle du récepteur CD36 de la microvasculature dans la régulation de la réponse inflammatoire. L’utilisation des ligands synthétiques du CD36 pourrait représenter une nouvelle avenue thérapeutique dans le traitement des réponses inflammatoires aiguës. / CD36 is a class B scavenger receptor expressed by multiple cell types such as macrophages and microvascular endothelial cells. CD36 shows a high affinity binding towards lipid-based ligands such as oxidized low-density lipoproteins (oxLDL). Macrophage CD36 has been shown to play a critical role in the development of atherosclerotic lesions by its ability to internalize oxLDL and to lead to foam cell formation. We tested the hypothesis that EP 80317, a selective CD36 ligand, exerts anti-atherosclerotic effects in apolipoprotein E-deficient (apoE–/–) mice fed on atherogenic diet. Long term treatment (12 weeks) with EP 80317 results in a striking reduction (51%) of lesion areas in EP 80317-treated apoE–/– mice. This effect was associated with a decrease in plasma cholesterol, a reduced oxLDL internalization within macrophages and an up-regulation of proteins involved in cholesterol efflux. Additionally, treatment with EP 80317 was associated with a reduced expression of vascular and plasma pro-inflammatory proteins. Our studies also showed a role of CD36 in modulating the recruitment of mononuclear phagocytes to the arterial wall, as shown by a reduced migration of radiolabeled CD36-/- macrophages into atherosclerotic lesions compared to CD36+/+ cells. At the molecular level, our studies showed that oxidized phospholipids induced the phosphorylation of the adhesion kinase Pyk2 in monocytes/macrophages, in a CD36- and Src-dependent manner. The Pyk2 phosphorylation is attenuated by treatment with EP80317. Our results strongly support the role of CD36 in atherosclerosis development and suggest that synthetic ligands featuring modulatory effect on CD36 function may represent a novel class of anti-atherosclerotic agents. CD36 expressed by microvascular endothelial cells is a receptor for the heterodimer S100A8/A9. These proteins bind intracellular arachidonic acid (AA) within polymorphonuclear neutrophils (PMN) and the complex S100A8/A9-AA may be secreted at sites of inflammation where it exerts chemotactic activities. We aimed to delineate the role of microvascular CD36, as a receptor for the S100A8/A9, in the AA transcellular metabolism and the regulation of the associated PMN trafficking to inflammatory sites. In two mouse models of acute inflammation (hind limb ischemia/reperfusion and dorsal air pouch), CD36 regulated trafficking of PMN to inflammatory sites, as shown by a mean of 63% reduction of PMN accumulation in CD36-/- mice. Treatment with EP 80317 or with S100A8/A9 antibodies reduced, each by ~ 60%, the recruitment of PMN to inflammatory sites. The combined administration of anti-S100A8/A9 and EP 80317 did not exert any additional inhibitory effect and neither treatment featured a modulatory effect in CD36-/- mice. Our results strongly support a role for microvascular CD36 in regulating PMN trafficking to inflammatory sites. Targeting CD36 might represent a novel therapeutic avenue for the treatment of acute inflammatory responses.

Diversas doenças estão associadas com a formação de novos vasos a parti vasos pré-existentes, ou angiogênese. Dentre elas está a aterosclerose (Griffioen & Molema, 2000). Pesquisas recentes demonstram que a hipercolesterolemia, que têm um papel importante na fisiologia da aterosclerose, também pode prejudicar a ação de fatores angiogênicos (Jang et.al., 2000). A hipercolesterolemia que é decorrente de aumento de LDL no plasma ocasiona um aumento no tempo de permanência desta partícula na circulação (Yasunobu, 2001). Contudo, a LDL pode sofrer modificação na circulação, dando origem a uma subfração mais eletronegativa da LDL, a LDL (-). A LDL (-) pode prejudicar cada etapa da angiogênese, desregulando a função endotelial (Tai et. al., 2006). Em nosso estudo, vimos que apesar da LDL (-) ter estimulado a miga celular, esta partícula inibiu a formação de túbulos in vitro. A LDL (-) não foi capa afetar a angiogênese in vivo. / A large number of diseases is associated with formation of new blood vessels out of pre-existing capillaries, or angiogenesis. These diseases include the atherosclerosis (Griffioen & Molema, 2000). Resents researches demonstrate that the hypercholesterolemia, that have a important role in the physiology of the atherosclerosis, can impaired the angiogenesis (Jang et. al., 2000) . The hypercholesterolemia that is decurrente of high levels of LDL in the plasma causes an increase in the time of permanence this particle in the circulation (Yasunobu, 2001). However, the LDL can to suffer modification in the circulation, giving rise to a subfration more eletronegative from LDL, the LDL (-). The LDL (-) could impair each one of the steps of the angiogenesis, thereby dysregulating endothelial function (Tai et. al., 2006). In our study, see that despite the LDL (-) have stimulated the cell migration, this particle inhibited the Tube formation in vitro. The LDL (-) didn\'t affect the angiogenesis in vivo.

Abstract Coronary heart disease (CHD) is a clinical manifestation of atherosclerosis. It is a major cause of mortality and morbidity both in Finland and globally. Even after the best known treatments a significant residual risk of CHD remains. A low plasma HDL cholesterol level (HDL, high-density lipoprotein) is a common lipid abnormality in patients affected by premature CHD and also a component of the metabolic syndrome, a cluster of risk factors for atherosclerosis associated with central obesity. In this study, a phenotype of low HDL cholesterol level and premature CHD was investigated in two Northern Finnish family populations. The aim was to find new biological factors accounting for the elevated CHD risk in the phenotype. In the subjects of family population I, plasma levels of antibodies (IgG, IgM, IgA) against experimental epitopes (malondialdehyde-acetaldehyde-modified, copper-oxidized) of oxidized LDL (low-density lipoprotein) particles were measured. In the subjects of family population II, capacity of HDL fractions (total HDL, HDL2 and HDL3) to accept cholesterol from a THP-1 experimental foam cell model was assayed (cholesterol efflux). In addition, a phospholipid composition of their HDL fractions (HDL2 and HDL3) was measured using liquid chromatography-mass spectrometry. The antibody levels were not related to CHD or to HDL cholesterol level. Instead, the cholesterol efflux to HDL2 fraction was clearly impaired in CHD, which was associated with the low HDL cholesterol level of the patients. The impaired cholesterol efflux to HDL2 fraction was primarily in conjunction with the metabolic syndrome. The phospholipid composition of HDL fractions was different between the affected and the non-affected subjects. As an example, characteristic of the metabolic syndrome were elevated contents of palmitic, palmitoleic or oleic acids relative to linoleic acid in lysophosphatidylcholines and phosphatidylcholines. In conclusion, the HDL fraction is both functionally and compositionally modified in the phenotype of low HDL cholesterol level and premature CHD. Especially the cholesterol efflux capacity of the HDL2 fraction and thus its many functional properties may be impaired. There are many characteristic features in the phospholipid composition of the HDL in the phenotype which were detected in HDL2 and HDL3 fractions. / Tiivistelmä Sepelvaltimotauti on ateroskleroosin kliininen ilmenemismuoto. Se on merkittävimpiä kuolleisuuden ja sairastavuuden aiheuttajia niin Suomessa kuin maailmalla. Parhaillakin tunnetuilla hoidoilla sepelvaltimotaudille jää huomattava jäännösriski. Plasman matala HDL-kolesterolitaso (HDL, high-density lipoprotein) on yleinen lipidipoikkeavuus varhaista sepelvaltimotautia sairastavilla ja myös eräs metabolisen oireyhtymän, eli keskivartalolihavuuteen liittyvän ateroskleroosin riskitekijäkasauman, komponentti. Tässä väitöskirjassa tutkittiin matalan HDL-kolesterolitason ja varhaisen sepelvaltimotaudin fenotyyppiä kahdessa pohjoissuomalaisessa sukuaineistossa. Tavoitteena oli löytää uusia biologisia tekijöitä fenotyypin kohonneen sepelvatimotautiriskin taustalta. Ensimmäisen aineiston henkilöiden plasmasta mitattiin vasta-ainetasoja (IgG, IgM, IgA) LDL-hiukkasten (LDL, low-density lipoprotein) kokeellisia hapettuneita epitooppeja (malonidialdehydi-asetaldehydi-modioitu ja kuparilla hapetettu LDL) vastaan. Toisessa aineistossa mitattiin henkilöiden HDL-fraktioiden (kokonais-HDL, HDL2 ja HDL3) kykyä saada aikaan kolesterolin ulosvirtausta kokeellisesta THP-1 vaahtosolumallista. Lisäksi heidän HDL-fraktioidensa (HDL2, HDL3) fosfolipidikoostumus mitattiin nestekromatografi-massaspektrometri-laitteistolla. Vasta-ainetasot eivät liittyneet sepelvaltimotautiin tai HDL-kolesterolitasoon. Sen sijaan kolesterolin ulosvirtaus HDL2-fraktioon oli selkeästi alentunut sepelvaltimotaudissa, mikä liittyi potilaiden pieneen HDL-kolesterolipitoisuuteen. Alentunut ulosvirtaus HDL2-fraktioon liittyikin ensisijaisesti metaboliseen oireyhtymään. HDL-fraktioiden fosfolipidikoostumus erosi terveiden ja sairaiden välillä. Esimerkiksi metabolisessa oireryhtymässä tunnusomaista oli lysofosfatidyylikoliinien ja fosfatidyylikoliinien sisältämän palmitiinihapon, palmitoleiinihapon tai oleiinihapon suurentunut määrä suhteessa niiden sisältämän linoleenihapon määrään. Loppupäätelmä on, että matalan HDL-kolesterolitason ja varhaisen sepelvaltimotaudin fenotyypin HDL-fraktio on sekä toiminnaltaan että koostumukseltaan muuntunut. Erityisesti HDL2-fraktion kyky saada aikaan kolesterolin ulosvirtausta ja näin ollen sen monet toiminnalliset ominaisuudet voivat olla alentuneet. Fenotyypin HDL:n fosfolipidikoostumuksessa on monia tunnusomaisia piirteitä, joita havaittiin sekä HDL2- että HDL3-fraktiossa.

Erkrankungen des Herz-Kreislaufsystems sind trotz erheblicher Fortschritte in Diagnostik und Therapie noch immer die häufigste Todesursache in Deutschland. Neben bekannte Risikofaktoren wie Hypercholesterinämie, Hyperlipoproteinämie, Diabetes mellitus, Adipositas, Bewegungsmangel, Stress und hohem Alter wird eine pathophysiologisch erhöhte Bildung reaktiver Sauerstoffspezies (ROS) als Ursache für deren Entstehung diskutiert. NAD(P)H-Oxidasen, von denen 7 Isoformen der katalytischen Nox-Untereinheiten bekannt sind, stellen dabei die Hauptquelle für vaskuläre Superoxidanionen und oxidativen Stress dar. In dieser Arbeit konnte die vorrangige Bedeutung eines intrazellulär lokalisierten Nox4-haltigen NAD(P)H-Oxidase-Komplexes für die konstitutive Radikalbildung in primären humanen Endothelzellen nachgewiesen werden. Weiterhin konnte gezeigt werden, dass durch chronische Applikation der biomechanischen Kräfte Schubspannung und Dehnung oxidativer Stress in humanen Endothelzellen in vitro vermindert werden kann. Die Herabregulation der Superoxidanionen-Bildung sowie die vermehrte Freisetzung von NO durch chronische Applikation biomechanischer Kräfte trägt zur positiven Balance von NO/Superoxidanionen und zum vasoprotektiven Potential physiologischer Schubspannung bzw. Dehnung bei. Durch Nox4-Promotordeletionsanalysen und Mutationsstudien konnte der Transkriptionsfaktor AP-1 als entscheidend für die schubspannungsabhängige Herabregulation von Nox4 identifiziert werden. Durch Stimulation von Endothelzellen bzw. murinen Gefäßringen mit oxidiertem LDL konnte dagegen die vaskuläre ROS-Bildung in vitro und ex vivo induziert werden. Zur weiteren Aufklärung des Mechanismus der LDL-induzierten ROS-Bildung in vivo und des Einflusses von NAD(P)H-Oxidasen wurden C57BL/6 (Wildtyp)- und Nox2-/--Mäuse 10 Wochen lang mit einer fettreichen Diät (Western diet) gefüttert und anschließend der Einfluss dieser Fütterung auf die NAD(P)H-Oxidase-Expression und ROS-Bildung analysiert. In der Aorta thoracalis beider Mausstämme zeigte sich durch das fettreiche Futter ein signifikanter Anstieg der NAD(P)H-Oxidase-Aktivität im Vergleich zum Standardfutter. Durch Western diet-Fütterung wurde die Nox4-mRNA-Expression in der A. thoracalis von Nox2-/--Mäuse und die p22phox-mRNA-Expression in beiden Mausstämmen induziert. Die Analyse weiterer Organe (Herz, Niere) zeigte keine Induktion von NAD(P)H-Oxidase-Untereinheiten durch Western diet-Fütterung. Zusammenfassend sprechen die Ergebnisse der vorliegenden Arbeit für eine entscheidende Rolle der Nox4-haltigen NAD(P)H-Oxidase bei der vaskulären Radikalbildung in vitro und in vivo. / Cardiovascular diseases are the most common causes of death in Germany. Beside the known risk factors hypercholesteremia, hyperlipoproteinemia, diabetes mellitus, obesity, sedentary lifestyle, stress and high age, a pathophysiologically increased formation of reactive oxygen species (ROS) are discussed as cause of development of cardiovascular diseases. Nicotine adenine dinucleotide phosphate (NADPH) oxidase complexes have been identified as main source of oxidative stress and vascular superoxide anions. There are 7 known isoforms of the catalytic Nox subunit of the NADPH oxidase. In this dissertation it was shown that NADPH oxidase subunit Nox4 is the major Nox isoform in human endothelial cells. Nox4 could be localized in the perinuclear space. Overexpression of Nox4 enhanced endothelial superoxide anion formation. Furthermore, a reduction of oxidative stress could be demonstrated by chronic application of the biomechanical forces laminar shear stress and cyclic strain in endothelial cells in vitro. The observed downregulation of superoxide anion formation and upregulation of NO formation by application of biomechanical forces contribute to the positive balance between NO and superoxide anion and the vasoprotective potential of physiological shear stress and cyclic strain. Molecular cloning and functional analysis of the human Nox4 promoter revealed that an AP-1 binding site is essential for downregulation of Nox4 by laminar shear stress. On the other hand stimulation of endothelial cells and murine vessels with oxidized lipids caused an upregulation of vascular ROS production in vitro and ex vivo. In order to examine the mechanism of LDL induced ROS formation and the influence of NADPH oxidase, C57BL/6 (wild-type) and Nox2-/- mice were feed with a diet high in fat and sugar (Western-type diet) for 10 weeks. After feeding, the influence of diet on the expression of NADPH oxidase and ROS production was analyzed in the A. thoracalis. Both mice strains showed a significant upregulation of aortic ROS production in comparison to normal chow. The mRNA expression of aortic Nox4 was induced in Nox2-/- mice. Furthermore, the aortic p22phox mRNA expression was upregulated in both mice strains. The analysis of other organs (heart, kidney) showed no influence of the Western-type diet. In conclusion, the results demonstrate a major role of a Nox4 containing NADPH oxidase in the vascular radical formation in vitro and in vivo.

Diversas doenças estão associadas com a formação de novos vasos a parti vasos pré-existentes, ou angiogênese. Dentre elas está a aterosclerose (Griffioen & Molema, 2000). Pesquisas recentes demonstram que a hipercolesterolemia, que têm um papel importante na fisiologia da aterosclerose, também pode prejudicar a ação de fatores angiogênicos (Jang et.al., 2000). A hipercolesterolemia que é decorrente de aumento de LDL no plasma ocasiona um aumento no tempo de permanência desta partícula na circulação (Yasunobu, 2001). Contudo, a LDL pode sofrer modificação na circulação, dando origem a uma subfração mais eletronegativa da LDL, a LDL (-). A LDL (-) pode prejudicar cada etapa da angiogênese, desregulando a função endotelial (Tai et. al., 2006). Em nosso estudo, vimos que apesar da LDL (-) ter estimulado a miga celular, esta partícula inibiu a formação de túbulos in vitro. A LDL (-) não foi capa afetar a angiogênese in vivo. / A large number of diseases is associated with formation of new blood vessels out of pre-existing capillaries, or angiogenesis. These diseases include the atherosclerosis (Griffioen & Molema, 2000). Resents researches demonstrate that the hypercholesterolemia, that have a important role in the physiology of the atherosclerosis, can impaired the angiogenesis (Jang et. al., 2000) . The hypercholesterolemia that is decurrente of high levels of LDL in the plasma causes an increase in the time of permanence this particle in the circulation (Yasunobu, 2001). However, the LDL can to suffer modification in the circulation, giving rise to a subfration more eletronegative from LDL, the LDL (-). The LDL (-) could impair each one of the steps of the angiogenesis, thereby dysregulating endothelial function (Tai et. al., 2006). In our study, see that despite the LDL (-) have stimulated the cell migration, this particle inhibited the Tube formation in vitro. The LDL (-) didn\'t affect the angiogenesis in vivo.