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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Syntéza stabilních analog O-acetyl-adenosin difosforibosy a inhibitorů sirtuinů / The synthesis of stable O-acetyl-adenosine diphosphoribose analogs and inhibitors of sirtuins

Dvořáková, Marcela January 2013 (has links)
Acetylated adenosine diphosphoribose (OAADPR) is a product of protein deacetylation catalysed by class III of histone deacetylases called sirtuins. Sirtuins deacetylate histones and other proteins by unique mechanism coupled with consumption of stoichiometric amount of NAD+ . Sirtuins and OAADPR are implicated in the regulation of gene transcription, signalling and metabolic pathways and lifespan extension, thus preventing the development of age-related diseases. Even though, sirtuins are well studied, the exact biological role of OAADPR remains mainly unknown. Its further exploration is restricted by OAADPR's proneness to enzymatic hydrolysis. Therefore, non-hydrolysable analogues of OAADPR are needed to establish its biological function. These analogues are also expected to be competitive inhibitors of sirtuins, which may reveal their potential as therapeutic agents. A series of OAADPR analogues in which the acetate moiety was replaced with alkylcarbonate functionality has been synthesized. The studies of alkylcarbonate migration on furanoside scaffold have established the stability of alkylcarbonate vs. acetate under various conditions. Generally, alkylcarbonates are more stable than acetate under acidic or neutral conditions whereas under basic conditions they seem to be less stable....
2

Avaliação da atividade anti-hRSV da quercetina e seus derivados acetilados / Evaluate anti-hRSV activity of quercetin and acetylated derivatives

Lopes, Bruno Rafael Pereira [UNESP] 16 March 2016 (has links)
Submitted by BRUNO RAFAEL PEREIRA LOPES null (brunorpl@hotmail.com) on 2016-05-11T19:53:59Z No. of bitstreams: 1 Dissertação versão repositório.pdf: 7264895 bytes, checksum: 0ac82b804ba7471cb20cb92afa6c4d3f (MD5) / Rejected by Felipe Augusto Arakaki (arakaki@reitoria.unesp.br), reason: Solicitamos que realize uma nova submissão seguindo as orientações abaixo: O arquivo submetido está sem a folha de aprovações providenciada pela Pós-graduação. Lembramos que a versão submetida por você é considerada a versão final da dissertação/tese, portanto não poderá ocorrer qualquer alteração em seu conteúdo após a aprovação. Corrija esta informação e realize uma nova submissão contendo o arquivo correto. Agradecemos a compreensão. on 2016-05-13T16:24:02Z (GMT) / Submitted by BRUNO RAFAEL PEREIRA LOPES null (brunorpl@hotmail.com) on 2016-05-16T19:16:16Z No. of bitstreams: 1 Dissertação numerado FINAL Capa Dura versão folha de aprovação.pdf: 7936969 bytes, checksum: b93b6e0c25c357b92f65cec6ffb9e789 (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2016-05-18T13:48:58Z (GMT) No. of bitstreams: 1 lopes_brp_me_assis.pdf: 7936969 bytes, checksum: b93b6e0c25c357b92f65cec6ffb9e789 (MD5) / Made available in DSpace on 2016-05-18T13:48:58Z (GMT). No. of bitstreams: 1 lopes_brp_me_assis.pdf: 7936969 bytes, checksum: b93b6e0c25c357b92f65cec6ffb9e789 (MD5) Previous issue date: 2016-03-16 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / No mundo, estima-se que exista cerca de 12 milhões de casos graves e 3 milhões de casos muito graves de infecção do trato respiratório inferior em crianças anualmente. Dentre os agentes etiológicos destas infecções, o vírus sincicial respiratório humano (hRSV) é a principal causa de internações infantis em países desenvolvidos, agravando os casos de bronquiolite, pneumonia e infecções pulmonares obstrutivas crônicas em pessoas de todas as idades, principalmente crianças e idosos. Estudos preliminares demonstraram que a Quercetina possui ação virucida sobre hRSV, além de inibir sua replicação. Entretanto, não se tem conhecimento do quão promissora é a atividade antiviral de Quercetina sobre o vírus hRSV ou mesmo se esta atividade poderia ser melhorada através de mudanças químicas em sua estrutura molecular. Assim, o objetivo deste trabalho foi estabelecer o índice de seletividade (IS) para Quercetina e seus derivados acetilados durante a infeção por hRSV através de ensaios in vitro. A análise de viabilidade celular através da adição do sal de MTT determinou os valores de CC50 para Quercetina na presença/ausência do vermelho de fenol (85 e 11,4 µM, respectivamente). Dentre as condições testadas, Quercetina apresentou atividade virucida (16-30% de proteção celular) sem apresentar efeitos no pré ou pós-tratamentos. Os valores de CC50 dos compostos derivados Q1 e Q2 foram 37,1 µM e 53,15 µM, respectivamente. O composto Q1 apresentou atividade anti-hRSV nos protocolos virucida e pós-tratamento (60-90%; 4-8 µM). O composto Q2 não apresentou atividade anti-hRSV relevante em nenhuma das condições testadas. A proteção celular apresentada pela Quercetina não possibilitou o cálculo de IS (CC50/CE50) o que nos sugere que este composto não seja um promissor agente anti-hRSV. Os índices de Seletividade calculados para o composto Q1 nos protocolos virucida e pós-tratamento foi de 9,27. O conjunto de resultados obtidos neste trabalho apresenta menor citotoxicidade e melhor performance anti-hRSV do composto Q1 em relação à Quercetina comercial. Estes dados nos estimulam a dar continuidade aos estudos do composto Q1 com o intuito de melhorarmos sua atividade antiviral e assim propormos um novo composto que seja efetivos na prevenção e/ou tratamento das infecções por hRSV. / Worldwide, is estimated that there are about 12 million serious cases and 3 million severe cases of lower respiratory tract infection in children every year. Among the etiological agents of these infections, respiratory syncytial virus (hRSV) is the leading cause of children's hospitalizations in developed countries, aggravating cases of bronchiolitis, pneumonia and chronic obstructive pulmonary infections in people of all ages, especially children and the elderly. Preliminary studies demonstrated that Quercetin has virucidal action on hRSV, and inhibits replication. However, we do not know how promising is the antiviral activity of Quercetin on the hRSV. The objectives of this work is to understand the action of Quercetin and some of its derivatives acetylated on the steps of the replicative cycle of hRSV, determining the selectivity index for each compound. The development of this project will assist in the search for effective compounds in the prevention and/or treatment of hRSV infections. In the cytotoxicity assays, Quercetin showed CC50 values variable depending on the presence/absence of phenol red (11.4 and 85 μM respectively). Among the concentrations tested Quercetin only showed a slight virucidal activity (16-30% concentration 5-10 μM). The CC50 values were derived compounds 37.1 μM for Q1 and Q2 to 53.15 μM. Compound Q1 showed anti-hRSV activity in virucidal and post-treatment protocol (60-90% at 4-8 μM). The Q2 compound showed no anti-hRSV relevant activity. The presence or absence of phenol red had great influence in determining the CC50 values of Quercetin (11.4 μM and 85 μM with phenol red). In addition, Quercetin showed little (virucidal protocol without phenol) or no anti-hRSV activity. Thus it has not been possible to establish the EC50 of Quercetin and determine its selectivity index (SI). The Q1 compound showed a greater CC50 value (37.1 μM) and relevant anti-hRSV activity in post-treatment and virucidal protocols (SI 9.27). Among the compounds tested, Q2 showed the highest value of CC50 (53.15 μM without phenol) however, had little or no anti-hRSV activity, making it impossible to determine their SI.
3

Human Monocyte Scavenger Receptors Are Pattern Recognition Receptors for (1→3)-β-D-Glucans

Rice, Peter J., Kelley, Jim L., Kogan, Grigorij, Ensley, Harry E., Kalbfleisch, John H., William Browder, I., Williams, David L. 01 July 2002 (has links)
Glucans are cell wall constituents of fungi and bacteria that bind to pattern recognition receptors and modulate innate immunity, in part, by macrophage activation. We used surface plasmon resonance to examine the binding of glucans, differing in fine structure and charge density, to scavenger receptors on membranes isolated from human monocyte U937 cells. Experiments were performed at 25°C using a biosensor surface with immobilized acetylated low density lipoprotein (AcLDL). Inhibition of the binding by polyinosinic acid, but not polycytidylic acid, confirmed the interaction of scavenger receptors. Competition studies showed that there are at least two AcLDL binding sites on human U937 cells. Glucan phosphate interacts with all sites, and the CM-glucans and laminarin interact with a subset of sites. Polymer charge has a dramatic effect on the affinity of glucans with macrophage scavenger receptors. However, it is also clear that human monocyte scavenger receptors recognize the basic glucan structure independent of charge.
4

Physical and Mechanical Properties of Medite® MDF Exterior from Acetylated Wood Fibers

Li, Junqiu January 2018 (has links)
Currently, the demand for wood-based panels has been growing solidly in European countries. Medium density fibreboard (MDF) manifests the potentialities for outstanding physical and mechanical properties. However, MDF from different fiber sources is normally designed for internal applications due to the poor moisture resistant capability. This study was conducted on acetylated MDF (Medite® MDF Exterior) to evaluate how physical (i.e. density, moisture content, dimensional stability, thickness swelling) and mechanical (i.e. modulus of elasticity, internal bonding strength before and after accelerated aging, bending stiffness and bending strength) properties behave at different relative humidity (i.e. 35 %, 65 % and 85 % RH at constant temperature of 20 ℃) levels. Bending stiffness was measured non-destructively by means of resonance method. The material used for control samples was commercial MDF. The size, quantity, conditioning and test method were followed in accordance with respective standards. The results showed that physical and mechanical properties were less influenced by Medite® MDF Exterior compared to commercial MDF. Medite® MDF Exterior were superior to commercial MDF in moisture resistance. Medite® MDF Exterior had more stable mechanical properties than commercial MDF with the changes of relative humidity.
5

Otimização da sintese de monoacilglicerois acetilados por via enzimaica / Otimizations of enzymatic synthesis of acetylated monoacylglycerols

Cruz, Carla Lea de Camargo Vianna 23 August 2007 (has links)
Orientador: Daniel Barrera Arellano / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-09T03:51:29Z (GMT). No. of bitstreams: 1 Cruz_CarlaLeadeCamargoVianna_D.pdf: 616206 bytes, checksum: 98da89ebbff6356a40ef492ce249aa2f (MD5) Previous issue date: 2007 / Resumo: Os monoacilgliceróis acetilados (MGA) são produtos de alto valor agregado utilizados em coberturas ou filmes comestíveis, gomas de mascar e produtos farmacêuticos entre outros. Esses são usualmente produzidos através de interesterificação química na presença de catalisadores ácidos ou básicos sob alta temperatura, acima de 200°C, consumindo grande quantidade de energia e produzindo compostos indesejáveis no produto. Além disso, há necessidade de se realizar uma destilação molecular para purificar o produto. A interesterificação enzimática ocorre em condições mais suaves eliminando tais problemas e o processo de purificação pode ser uma destilação simples. Este estudo apresenta um processo de obtenção de MGA via enzimática através de reação de interesterificação, e subseqüente destilação. Foram realizados testes para selecionar os substratos e via de processo com ácido oléico, óleo de soja e gordura parcialmente hidrogenada de soja esterificados com triacetina em diferentes proporções. Foram testadas quatro enzimas diferentes Lipozyme TL 100L, Lipozyme IM, Lipozyme RM IM e Lipozyme TL IM. Após seleção da enzima (Lipozyme TL IM) e substrato (gordura parcialmente hidrogenada) foi realizada a otimização utilizando um desenho experimental fatorial completo 23, totalizando 17 ensaios, sendo 3 pontos centrais e 6 axiais. As variáveis independentes foram: tempo (h), temperatura (°C) e quantidade da enzima (% em relação ao total dos substratos). As variáveis dependentes: rendimento de MGA (%) e relação diacilglicerol/monoacilglicerol, foram determinadas por HPSEC (High Performance Size Exclusion Chromatography). A faixa ótima encontrada foi: 6 horas, 65°C e 4% de enzima em relação ao total de substratos. Nestas condições foi possível produzir MGA em concentrações até 85% após destilação. Testes de reutilização da enzima, com 0,4% de enzima nova adicionados em cada ciclo indicam que após 6 ciclos essa mantém alta atividade. O produto purificado apresentou características similares ao produto comercial / Abstract: Acetylated monoacylglycerols (AMG) are high added value products used in coatings or edible films, bubble gums, pharmaceutical products and others. They are usually produced through chemical interesterification, in the presence of acid or basic catalysts at high temperatures (above 200°C), causing high energy demands, producing undesirable by-products and requiring molecular distillation to purify the product. Enzymatic interesterification occurs in mild conditions, eliminating such problems, and the purification process can be a simple distillation. This study presents an enzymatic process to obtain AMG through the interesterification reaction and subsequent distillation. Trials were carried out to select the substrates and process path using oleic acid, soy oil and partially hydrogenated soy fat, esterified with triacetin in different proportions (1:1.5 and 1:3). Four different enzymes were tested: Lipozyme TL 100L, Lipozyme IM, Lipozyme RM and Lipozyme TL IM. After the selection of the enzyme (Lipozyme TL IM) and the substrate (partially hydrogenated fat), the optimization of the reaction was studied using a 23 complete factorial experimental design, totalizing 17 assays, including 3 central and 6 axial points. The independent variables were: time (h), temperature (°C) and quantity of enzyme (% of total substrates). The dependent variables were: AMG yield (%) and diacylglycerol/monoacylglycerol ratio, analyzed through HPSEC (High Performance Size Exclusion Chromatography). The optimal condition found was 6 hours, 65°C and 4% enzyme with respect to total substrates. Under these conditions, it was possible to produce AMG in concentrations of up to 85% after distillation. Enzyme reutilization trials, adding 0.4% new enzyme to each cycle, indicate that, after 6 cycles, high enzyme activity is maintained. The purified product presented characteristics similar to the commercial product / Doutorado / Doutor em Tecnologia de Alimentos
6

Studies on Biological Properties of a Novel Repellent, Acetylated Glyceride, against Adult Sweet potato Whitefly Bemisia tabaci (Hemiptera: Aleyrodidae) / 新規コナジラミ類成虫忌避剤アセチル化グリセリドの生物作用特性に関する研究

Kashima, Takayuki 23 March 2016 (has links)
Rights to some articles appeared in this disseration are reserved by the ELSEVIER B.V., John Wiley & Sons, Inc. and Pesticide Science Society of Japan.If any of these materials you wish to use, authorisation from sources must be obtain. / 京都大学 / 0048 / 新制・論文博士 / 博士(農学) / 乙第13023号 / 論農博第2833号 / 新制||農||1043(附属図書館) / 学位論文||H28||N4968(農学部図書室) / 32951 / (主査)教授 佐久間 正幸, 教授 松浦 健二, 教授 奥野 哲郎 / 学位規則第4条第2項該当 / Doctor of Agricultural Science / Kyoto University / DFAM
7

Vrstvy oxidu wolframového připravené z nanočásticových suspenzí a pojiva / Tungsten trioxide coatings fabricated from nanocrystalline suspension and binder

Filipská, Markéta January 2021 (has links)
This diploma thesis deals with layers of tungsten oxide, which are prepared from a nanoparticle suspension and a binder. The coating composition consisted in the first case of ground tungsten oxide nanoparticles alone, then of acetylated peroxotungstic acid alone and finally of a mixture of ground tungsten oxide mixed with acetylated peroxotungstic acid. The compositions thus formed were applied to conductive FTO glass and thus act as photoanodes. A stainless steel needle is used as a counter electrode for volt-ampere measurements. The work focuses on the study of physicochemical properties of prepared photoanodes and their optimalization in order to obtain the highest possible values of generated photocurrents. The electrical properties of all cells were determined using voltammetric characteristics.
8

Finger-jointing of acetylated Scots pine using a conventional MUF resin

Wincrantz, Christian January 2018 (has links)
Acetylation of wood is a modification technique that chemically alters the wood substance and enhances several properties of wood. The basic principle is to impregnate wood with acetic anhydride to react and replace OH-groups with acetyl groups in the wood cell wall. In this way, the hygroscopicity of the modified wood is significantly reduced resulting in increased dimensional stability and durability compared with unmodified wood.The objective of this work was to study finger-jointing of acetylated Scots pine (Pinus sylvestris L.) using a conventional melamine urea formaldehyde (MUF) adhesive. Two different types of acetylated pine specimens were investigated, acetylated pine sapwood (APS) and acetylated juvenile pine (AJP), the latter originating from young forest thinning trees (ca 20-30 years). The goal was to evaluate the bending strength, i.e. modulus of rupture (MOR), of such finger-jointed samples, in particular when the acetylated wood was combined with unmodified wood, in this case, Norway spruce (Picea Abies L. Karst) (US). The finger-jointing were performed at Moelven Töreboda by applying their existing industrial procedures. In total, five different of finger jointed sample groups were prepared combining the different specimens: APS-APS, AJP-AJP, US-US, APS-US, and AJP-US. Standardized procedures were used to determine the MOR of the finger-jointed samples, both unexposed at the factory condition state and after a water-soaking-drying cycle. In addition, the experiments also included determination of the moisture content (MC), density, and modulus of elasticity (MOE) (in bending along the grain) of the individual specimens.At the unexposed state, the APS-APS samples showed the highest MOR of 63,1 MPa, while those of the AJP-AJP showed the lowest value of 42,4 MPa. The corresponding values for the US-US, AJP-US and APS-US samples was 56,7, 47,5 and 46,9 MPa, respectively. In contrast to a typical wood failure for the US-US samples, a low amount of wood failure was observed in all cases involving the acetylated wood, indicating a low adhesive anchoring in the wood substrate at the finger-joint, although a surprisingly high strength was obtained for the APS-APS samples. A significantly lower MC content of 4,9 % and a remarkably low value of 1,7 %, was found for the APS and AJP, respectively, compared with 9,2% for the US. The significantly lower MC combined with an assumed increased hydrophobicity of the acetylated wood possible causes a less effective MUF-wood bonding, or adhesion, compared with that of the unmodified wood. Possible, so-called over penetration of the MUF resin in the acetylated wood could also be an explanation for the poor wood-adhesive anchoring. The MOE of the individual APS, AJP and US specimens was 12,6, 8,3 and 11,4 GPa, respectively, indicating a significantly lower mechanical performance of AJP, and hence also of finger-joints of AJP, despite its very low MC, possible due to a higher microfibril angle in the cell walls in juvenile wood compared with mature wood. No clear correlation was found between the MOR and density of the acetylated samples.For the samples exposed to a water-soak-drying cycle, the highest MOR, and lowest reduction of 14 % compared with the unexposed state, was obtained for the US-US samples, whereas all samples involving the acetylated wood showed a distinctly higher reduction. The MOR of the AJP-AJP and AJP-US samples were reduced with 47 % and 50 %, respectively, while the MOR of the APS-APS and APS-US samples were reduced with 43 % and 23 %, respectively. It should be emphasized, however, that after the standard drying-time, which was the same for all samples, the acetylated samples, compared with the untreated ones, did not dry out to the same level as for the dry unexposed state, i.e. the acetylated samples had a high MC of ca 30-40% in these MOR tests. This high MC level could be the main reason for the dramatic strength losses. Furthermore, a less efficient wood-MUF adhesion as well as the drying under acidic conditions may also be possible causes for the reduced bending strength of the finger-jointed samples with acetylated wood.
9

Influence des amidons natifs ou acétylés de manioc et de pomme de terre sur les propriétés physico-chimiques et texturales du pâté de Boeuf (Bos indicus) / Effect of native or acetylated cassava and potatoes starches on physico chemical and textural properthes ofBeef patties

Mbougueng, Pierre Désiré 21 January 2009 (has links)
Pour cette étude, dans un premier temps, une caractérisation physico-chimique et rhéologique des amidons natifs de deux cultivars locaux de pomme de terre (Sipiera et Tselefou) et de trois de manioc (2425, 4115 et Seedling) a été faite avant leur incorporation dans du pâté de bœuf à 20, 30, 40 et 50g/kg de mêlée. L’influence du type d’amidon et de leur taux d’incorporation sur les propriétés physico-chimiques et texturales des pâtés a été évaluée. Les résultats ont montré que les propriétés physiques, fonctionnelles et rhéologiques des amidons sont étroitement liées à leur origine botanique. L’Analyse en Composantes Principales (ACP) laisse paraître que de tous les amidons natifs, celui du cultivar de pomme de terre Sipiera se rapproche le plus du témoin. Une fois incorporé dans les pâtés ; l’ACP de tous les paramètres texturaux des pâtés aux amidons natifs indique que le pâté à l’amidon du cultivar de manioc Seedling à de 40g/kg de mêlée (PS40), est celui qui se rapproche le plus du pâté témoin. Dans un deuxième temps, les amidons de pomme de terre (Sipiera) et de manioc (2425) ont été sélectionnés pour la modification (acétylation). Ces amidons acétylés ont par la suite fait l’objet des mêmes analyses que les amidons natifs et incorporés dans les pâtés aux mêmes taux que les amidons natifs. Des résultats, il ressort que les propriétés fonctionnelles des amidons natifs sont fortement influencées par l’acétylation et le temps d’acétylation. Les essais d’incorporation des amidons acétylés dans les pâtés montrent que l’amidon Sipiera/20 à un taux d’incorporation de 40g/kg de mêlée ne se distingue pas significativement (p>0,05) du pâté témoin / The first part of this work deals with the physico-chemical and rheological characterisation of native starches of two local cultivars of Irish potatoes (Sipiera and Tselefou) and three cultivars of cassava (2425, 4115 and Seedling) before they are incorporated into beef patty at 20, 30, 40 and 50g/kg ground meat. The influence of the type of starch and the amount of incorporation on the physico-chemical and textural properties of patties was evaluated. Results show that the physical, functional and rheological properties of starches are closely related to their botanical origin. Principal Component Analysis (PCA) showed that Irish potato cultivar Sipiera had properties that were close to reference. The PCA of all the textural properties of patties with native starches show that patty from starch of cassava cultivar Seedling at 40g/kg (PS40) was closest to the reference. In the second part of the work, the starch Sipiera and 2425 were selected for modification. These two starches were then acetylated for 10 and 20min. and this permitted us to have Sipiera/10, Sipiera/20, 2425/10 and 2425/20. The functional properties of the native starches were however strongly influenced by acetylation and the time of acetylation. Incorporation trials of this acetylated starches at different amounts in patty showed that Sipiera/20 starch at an incorporation rate of 40g/kg ground meat is not significantly different from the reference patty
10

The Role of Scavenger Receptor-A in Heat Shock Protein 27-mediated Atheroprotection: Mechanistic Insights into a Novel Anti-atherogenic Therapy

Raizman, Joshua E. 03 May 2012 (has links)
Heat shock protein (HSP)27 is traditionally described as an intracellular chaperone and signaling molecule, but growing evidence suggests it is released from immune cells where it plays an anti-inflammatory role during atherogenesis. Previously, the O’Brien lab found that overexpression of HSP27 led to augmented HSP27 serum levels in female apolipoprotein E knockout (ApoE-/-) mice, attenuated atherogenesis, and inhibited macrophage foam cell formation via physical binding with scavenger receptor (SR)-A. However, the precise mechanism of atheroprotection remained elusive. This thesis sought to ascertain the mechanism(s) by which HSP27 prevents foam cell formation, and determine if SR-A, a key receptor involved in the uptake of lipid into macrophages, plays an important role in HSP27-mediated atheroprotection. Pre-treatment of human macrophages with recombinant HSP27 (rHSP27) inhibited acytelated low density lipoprotein (acLDL) binding and uptake independent from receptor competition effect. Reduction in uptake was associated with attenuation of expression of SR-A mRNA, total protein, and cell surface expression. To explore the signaling mechanism by which HSP27 modulated SR-A expression it was hypothesized that nuclear factor-kappa B (NF-kB), a major regulator of many atherosclerosis gene programs, is altered by extracellular HSP27. Indeed, rHSP27 markedly activated NF-kB signaling in macrophages. Using an inhibitor of NF-kBsignaling there was an attenuation of rHSP27-induced inhibition of SR-A gene and protein expression, as well as lipid uptake, suggesting that SR-A expression is regulated by NF-kB activation. Lastly, to investigate if SR-A is required for HSP27-mediated atheroprotection in vivo, ApoE-/- and ApoE-/-SR-A-/- mice fed a high fat diet were treated with rHSP25, the mouse orthologue of HSP27, or PBS for 3 weeks. While rHSP25 therapy equally reduced serum cholesterol levels in the mouse cohorts, aortic atherogenesis, assessed using en face and sinus cross-sectional analyses, was attenuated in ApoE-/- mice but not ApoE-/-SR-A-/- mice. In conclusion, rHSP27 inhibits foam cell formation by downregulating SR-A expression. This effect may be associated with NF-kB activation. Reductions in atherosclerotic burden by rHSP27 require SR-A, and are independent of changes in serum cholesterol levels, highlighting the importance of macrophage lipid uptake in atherogenesis. Results presented in this thesis demonstrate that SR-A is a major target for HSP27 atheroprotection in the vessel wall, and provide an impetus for further studies that investigate the potential therapeutic value of HSP27.

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