Mycoplasmal lipid-associated membrane proteins and Mycoplasma arthritidis mitogen recognition by serum antibodies from patients with rheumatoid arthritis

Mycoplasmal lipid-associated membrane proteins (LAMPs) and Mycoplasma arthritidis mitogen (MAM superantigen) are potent stimulators of the immune system. The objective of this work was to detect antibodies to MAM and LAMPs of Mycoplasma hominis and M. fermentans in the sera of patients affected by rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) to identify mycoplasmal products that can be involved in the etiopathogenesis of these autoimmune diseases. Serum samples from female RA and SLE patients and controls, recombinant MAM, and LAMPs of M. hominis PG21 and M. fermentans PG18 were used in Western blot assays. A similar frequency of sera from patients and controls reactive to MAM was detected. A larger number of M. hominis and M. fermentans LAMPs were recognized by sera from RA patients than controls, but no differences were detected between sera from SLE patients and controls. Among the LAMPs recognized by IgG antibodies from RA patients, proteins of molecular masses in a range of < 49 and a parts per thousand yen20 KDa (M. hominis) and < 102 and a parts per thousand yen58 KDa (M. fermentans) were the most reactive. These preliminary results demonstrate the strong reactivity of antibodies of RA patients with some M. hominis and M. fermentans LAMPs. These LAMPs could be investigated as mycoplasmal antigens that can take part in the induction or amplification of human autoimmune responses.

Differential expression of cytokines, chemokines and chemokine receptors in patients with coronary artery disease

Monocytes/macrophages and lymphocytes have a key role in the pathogenesis of atherosclerosis through the production of inflammatory and anti-inflammatory cytokines. We evaluated mRNA expression and protein production of CCL2, CXCL8, CXCL9, CXCL10, IFN-gamma and IL-10 in vitro as well as the expression of the CCR2 and CXCR3 receptors in peripheral blood mononuclear cells (PBMCs) of patients with coronary artery disease (CAD) and healthy controls in the presence or absence of oxidized LDL (oxLDL). Patients with CAD showed higher constitutive expression of CCL2, CXCL8, CXCL9, CXCL10 and IFN-gamma mRNA and, after stimulation with oxLDL, higher expression of CCL2 and CXCL8 mRNA than the control group. We also detected higher levels of CCL2 and CXCL8 in supernatants of oxLDL-stimulated PBMCs from CAD patients than in corresponding supernatants from controls. Patients with CAD had a higher percentage of constitutive CCR2(+) and CXCR3(+) cells after stimulation with oxLDL. Among CAD patients, the main differences between the stable (SA) and unstable angina (UA) groups were lower IL-10 mRNA production in the latter group. Altogether, our data suggest that PBMCs from CAD patients are able to produce higher concentrations of chemokines and cytokines involved in the regulation of monocyte and lymphocyte migration and retention in atherosclerotic lesions. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Vitellin-binding proteins in the nematode Oscheius tipulae (Nematoda, Rhabditida)

We describe the first application of a non-radioactive ligand-blotting technique to the characterization of proteins interacting with nematode vitellins. Chromatographically purified vitellins from the free-living nematode Oscheius tipulae were labeled with fluorescein in vitro. Ligand-blotting assays with horseradish peroxidase-conjugated anti-fluorescein antibodies showed that labeled vitellins reacted specifically with a polypeptide of approximately 100 kDa, which we named P100. This polypeptide is a specific worm`s vitellin-binding protein that is present only in adult worms. Blots containing purified O. tipulae vitellin preparations showed no detectable signal in the 100 kDa region, ruling out any possibility of yolk polypeptides self-assembling under the conditions used in our assay. Experiments done in the presence of alpha-methyl mannoside ruled out the possibility of vitellins binding to P100 through mannose residues. Triton X-114 fractionation of whole worm extracts showed that P100 is either a membrane protein or has highly hydrophobic regions. (C) 2008 Elsevier Inc. All rights reserved.

Putative outer membrane proteins of Leptospira interrogans stimulate human umbilical vein endothelial cells (HUVECS) and express during infection

Cell adhesion molecules (CAMs) are surface receptors present in eukaryotic cells that mediate cell-cell or cell-extracellular matrix interactions. Vascular endothelium stimulation in vitro that lead to the upregulation of CAMs was reported for the pathogenic spirochaetes, including rLIC10365 of Leptospira interrogans. In this study, we report the cloning of LIC10507, LIC10508, LIC10509 genes of L interrogans using Escherichia coli as a host system. The rational for selecting these sequences is due to their location in L. interrogans serovar Copenhageni genome that has a potential involvement in pathogenesis. The genes encode for predicted lipoproteins with no assigned functions. The purified recombinant proteins were capable to promote the upregulation of intercellular adhesion molecule 1 (ICAM-1) and E-selectin on monolayers of human umbilical vein endothelial cells (HUVECS). In addition, the coding sequences are expressed in the renal tubules of animal during bacterial experimental infection. The proteins are probably located at the outer membrane of the bacteria since they are detected in detergent-phase of L interrogans Triton X-114 extract. Altogether our data suggest a possible involvement of these proteins during bacterial infection and provide new insights into the role of this region in the pathogenesis of Leptospira. (C) 2008 Elsevier Ltd. All rights reserved.

Analytical quantification of low-density lipoprotein using europium tetracycline indicator

Low-density lipoprotein (LDL) is known as `bad` cholesterol. If too much LDL circulates in the blood it can be retained in the walls of the arteries, causing atherosclerosis. In this paper we showed an alternative method to quantify LDL using the europium tetracycline (EuTc) indicator. The optical properties of the EuTc complex were investigated in aqueous solutions containing LDL. An enhancement was observed of the europium luminescence in the solutions with LDL compared those without the lipoprotein. A method to quantify the amount of LDL in a sample, based on EuTc enhanced luminescence, is proposed. The enhancement mechanism is also discussed. Copyright (C) 2009 John Wiley & Sons, Ltd.

Cardiovascular Disease Parameters in Periodontitis

Background: Recently, there has been an increasing in the impact of oral health on atherosclerosis and subsequent cardiovascular disease. The aim of this study is to investigate the association between chronic periodontitis and cardiovascular risk markers. Methods: Forty patients with periodontitis and 40 healthy gender-, body mass index-, and age-matched individuals were compared by measuring total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, levels of cytokines, antibodies against oxidized low-density lipoprotein, thiobarbituric acid reactive substances, total and differential white blood cell counts, and the non-linear index of refraction. Results: The levels of triglycerides and high-density lipoprotein in periodontitis patients were significantly higher and lower, respectively (P=0.002 and P=0.0126), compared to controls. Total cholesterol, low-density lipoprotein, and lipid peroxide levels were the same in both groups (P = 0.2943, P = 0.1284, and P = 0.067, respectively). Interleukin (IL)-6 and -8, antibodies against oxidized low-density lipoprotein, and leukocyte and neutrophil counts were significantly higher in periodontitis patients (P<0.05). The value of the non-linear index of refraction of low-density lipoprotein solutions was higher in the controls (P = 0.015) compared to individuals with periodontitis. Conclusion: Our results confirmed and further strengthened the suggested association between coronary artery disease and periodontitis. J Periodontol 2009;80:378-388.

Differences and similarities of postprandial lipemia in rodents and humans

Background: The rat has been a mainstay of physiological and metabolic research, and more recently mice. This study aimed at characterizing the postprandial triglyceride profile of two members of the Muridae family: the Wistar rats (Rattus norvegicus albinus) and C57BL/6 mice (Mus musculus) plus comparing them to the profile obtained in humans. Methods: Thirty-one male and twelve female Wistar rats, ten C57BL/6 male and nine female mice received a liquid meal containing fat (17%), protein (4%) and carbohydrates (4%), providing 2 g fat/Kg. Thirty-one men and twenty-nine women received a standardized liquid meal containing fat (25%), dextromaltose (55%), protein (14%), and vitamins and minerals (6%), and providing 40 g of fat per square meter of body surface. Serial blood samples were collected at 2, 4, 6, 8 and 10 h after the ingestion in rats, at 1, 2, 3, 4, 5 and 6 h in mice and in humans at 2, 4, 6 and 8 h. Wilcoxon and Mann-Whitney tests were used. Results/Discussion: The triglyceride responses were evaluated after the oral fat loads. Fasting and postprandial triglyceridemia were determined sequentially in blood sample. AUC, AUIC, AR, RR and late peaks were determined. Conclusions: Rats are prone to respond in a pro-atherogenic manner. The responses in mice were closer to the ones in healthy men. This study presents striking differences in postprandial triglycerides patterns between rats and mice not correlated to baseline triglycerides, the animal baseline body weight or fat load in all animal groups.

Cathepsin S as a biomarker of low-grade inflammation, insulin resistance, and cardiometabolic disease risk

Cathepsin S is a protease important in major histocompatibility complex (MHC) class II antigen presentation and also in degrading the extracellular matrix. Studies, most of them experimental, have shown that cathepsin S is involved in different pathological conditions such as obesity, inflammation, atherosclerosis, diabetes, and cancer.    The overall hypothesis of this report is that high levels of circulating cathepsin S, is a biomarker that reflects pathology induced by inflammation and obesity. The overall aim of this report was to investigate possible associations between circulating cathepsin S, inflammation, glucometabolic disturbance, and its associated diseases in the community. As cathepsin S appears to be a novel risk marker for several pathological conditions, we also wanted to examine the effect of dietary intervention on circulating cathepsin S concentrations.    This thesis is based on data from three community-based cohorts, the Uppsala longitudinal study of adult men (ULSAM), the prospective investigation of the vasculature in Uppsala seniors (PIVUS), and a post-hoc study from the randomized controlled NORDIET trial.    In the first study, we identified a cross-sectional positive association between serum cathepsin S and two markers of cytokine-mediated inflammation, CRP and IL-6. These associations were similar in non-obese individuals. In longitudinal analyses, higher cathepsin S at baseline was associated with higher CRP and IL-6 levels after six years of follow-up. In the second study, we identified a cross-sectional association between increased serum levels of cathepsin S and reduced insulin sensitivity. These associations were similar in non-obese individuals. No significant association was observed between cathepsin S and insulin secretion. In longitudinal analysis, higher cathepsin S levels were associated with an increased risk of developing diabetes during the six-year follow-up. In the third study, we found that higher serum levels of cathepsin S were associated with increased mortality risk. Moreover, in the ULSAM cohort, serum cathepsin S was independently associated with cause-specific mortality from cardiovascular disease and cancer. In the fourth study, we identified that adherence to an ad libitum healthy Nordic diet for 6 weeks slightly decreased the levels of plasma cathepsin S in normal or marginally overweight individuals, relative to the control group. Changes in circulating cathepsin S concentrations were correlated with changes in body weight, LDL-C, and total cholesterol.    Conclusion: This thesis shows that circulating cathepsin S is a biomarker that independently reflects inflammation, insulin resistance, the risk of developing diabetes, and mortality risk. Furthermore, a Nordic diet moderately reduced cathepsin S levels in normal-weight and overweight men and women. This effect may be partially mediated by diet-induced weight loss and possibly by reduced LDL-C concentrations. 

Inflammation, oxidative stress, glomerular filtration rate, and albuminuria in elderly men : a cross-sectional study

BACKGROUND: The role of inflammation and oxidative stress in mild renal impairment in the elderly is not well studied. Accordingly, we aimed at investigating the associations between estimated glomerular filtration rate (eGFR), albumin/creatinine ratio (ACR), and markers of different inflammatory pathways and oxidative stress in a community based cohort of elderly men. FINDINGS: Cystatin C-based GFR, ACR, and biomarkers of cytokine-mediated inflammation (interleukin-6, high-sensitivity C-reactive protein[CRP], serum amyloid A[SAA]), cyclooxygenase-mediated inflammation (urinary prostaglandin F2alpha [PGF2alpha]), and oxidative stress (urinary F2 isoprostanes) were assessed in the Uppsala Longitudinal Study of Adult Men(n = 647, mean age 77 years). RESULTS: In linear regression models adjusting for age, BMI, smoking, blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, and treatment with statins, ACE-inhibitors, ASA, and anti-inflammatory agents, eGFR was inversely associated with CRP, interleukin-6, and SAA (beta-coefficient -0.13 to -0.19, p < 0.001 for all), and positively associated with urinary F2-isoprostanes (beta-coefficient 0.09, p = 0.02). In line with this, ACR was positively associated with CRP, interleukin-6, and SAA (beta- coefficient 0.09-0.12, p < 0.02 for all), and negatively associated with urinary F2-isoprostanes (beta-coefficient -0.12, p = 0.002). The associations were similar but with lower regression coefficients in a sub-sample with normal eGFR (>60 ml/min/1.73 m2, n = 514), with the exception that F2-isoprostane and SAA were no longer associated with eGFR. CONCLUSION: Our data indicate that cytokine-mediated inflammation is involved in the early stages of impaired kidney function in the elderly, but that cyclooxygenase-mediated inflammation does not play a role at this stage. The unexpected association between higher eGFR/lower albuminuria and increased F2-isoprostanes in urine merits further studies.

Influence of a prudent diet on circulating cathepsin S in humans

BACKGROUND: Increased circulating cathepsin S levels have been linked to increased risk of cardiometabolic diseases and cancer. However, whether cathepsin S is a modifiable risk factor is unclear. We aimed to investigate the effects of a prudent diet on plasma cathepsin S levels in healthy individuals. FINDINGS: Explorative analyses of a randomized study were performed in 88 normal to slightly overweight and hyperlipidemic men and women (aged 25 to 65) that were randomly assigned to ad libitum prudent diet, i.e. healthy Nordic diet (ND) or a control group (habitual Western diet) for 6 weeks. Whereas all foods in the ND were provided, the control group was advised to consume their habitual diet throughout the study. The ND was in line with dietary recommendations, e.g. low in saturated fats, sugars and salt, but high in plant-based foods rich in fibre and unsaturated fats.The ND significantly decreased cathepsin S levels (from 20.1 (+/-4.0 SD) to 19.7 μg/L (+/-4.3 SD)) compared with control group (from 18.2 (+/-2.9 SD) to 19.1 μg/L (+/-3.8 SD)). This difference remained after adjusting for sex and change in insulin sensitivity (P = 0.03), and near significant after adjusting for baseline cathepsin S levels (P = 0.06), but not for change in weight or LDL-C. Changes in cathepsin S levels were directly correlated with change in LDL-C. CONCLUSIONS: Compared with a habitual control diet, a provided ad libitum healthy Nordic diet decreased cathepsin S levels in healthy individuals, possibly mediated by weight loss or lowered LDL-C. These differences between groups in cathepsin S were however not robust and therefore need further investigation.

Role of dietary fats in modulating cardiometabolic risk during moderate weight gain : a randomized double-blind overfeeding trial (LIPOGAIN study)

BACKGROUND: Whether the type of dietary fat could alter cardiometabolic responses to a hypercaloric diet is unknown. In addition, subclinical cardiometabolic consequences of moderate weight gain require further study. METHODS AND RESULTS: In a 7-week, double-blind, parallel-group, randomized controlled trial, 39 healthy, lean individuals (mean age of 27±4) consumed muffins (51% of energy [%E] from fat and 44%E refined carbohydrates) providing 750 kcal/day added to their habitual diets. All muffins had identical contents, except for type of fat; sunflower oil rich in polyunsaturated fatty acids (PUFA diet) or palm oil rich in saturated fatty acids (SFA diet). Despite comparable weight gain in the 2 groups, total: high-density lipoprotein (HDL) cholesterol, low-density lipoprotein:HDL cholesterol, and apolipoprotein B:AI ratios decreased during the PUFA versus the SFA diet (-0.37±0.59 versus +0.07±0.29, -0.31±0.49 versus +0.05±0.28, and -0.07±0.11 versus +0.01±0.07, P=0.003, P=0.007, and P=0.01 for between-group differences), whereas no significant differences were observed for other cardiometabolic risk markers. In the whole group (ie, independently of fat type), body weight increased (+2.2%, P<0.001) together with increased plasma proinsulin (+21%, P=0.007), insulin (+17%, P=0.003), proprotein convertase subtilisin/kexin type 9, (+9%, P=0.008) fibroblast growth factor-21 (+31%, P=0.04), endothelial markers vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin (+9, +5, and +10%, respectively, P<0.01 for all), whereas nonesterified fatty acids decreased (-28%, P=0.001). CONCLUSIONS: Excess energy from PUFA versus SFA reduces atherogenic lipoproteins. Modest weight gain in young individuals induces hyperproinsulinemia and increases biomarkers of endothelial dysfunction, effects that may be partly outweighed by the lipid-lowering effects of PUFA. CLINICAL TRIAL REGISTRATION URL: http://ClinicalTrials.gov. Unique identifier: NCT01427140.

Estudo da influência da variabilidade em genes de apolipoproteínas sobre níveis lipídicos e parâmetros de massa e gordura corporal na população de Porto Alegre

Apolipoproteínas constituem a parte proteica das lipoproteínas e de uma maneira geral desempenham papéis como proporcionar estabilidade estrutural, solubilizar lipídeos altamente hidrofóbicos, servir como ligantes a receptores ou agir como co-fatores para enzimas envolvidas no metabolismo. Diversos estudos têm mostrado que a variabilidade dos genes que codificam estas proteínas podem influenciar os níveis lipídicos em diversas populações. A variabilidade da apo A-IV também foi associada com variáveis antropométricas. Nesta investigação foram analisados 8 RFLPs nos genes das apolipoproteínas C-I (HpaI), C-II (AvaII), C-III (SacI, FokI e MspI) e A-IV (XbaI, HinfI e PvuII). A amostra foi composta por 391 indivíduos caucasóides de Porto Alegre (RS) e dados sobre hábitos de vida, dosagens lipídicas e medidas antropométricas foram obtidas para cada indivíduo. Os fragmentos de interesse de cada gene foram amplificados por PCR e os genótipos foram identificados por eletroforese em géis de agarose ou poliacrilamida corados com brometo de etídio.

Níveis de lipoproteínas e apolipoproteínas em uma amostra de indivíduos descendentes de Japoneses da região de Cascavel (PR)

Dislipidemia são alterações nas concentrações dos lipídios no organismo, e são divididos em hipo e hiperlipidemias. As hiperlipidemias possuem maior importância clínica, frequentemente associadas com um aumento no risco em desenvolver outras doenças, como doenças coronarianas, pancreatites, etc. Altas concentrações dos lipídios plasmáticos, principalmente colesterol total, estão associados com doenças coronarianas. Altos níveis de triglicerídios e baixos níveis de HDL-colesterol, também são fatores que predispõem a doenças cardiovasculares. Os níveis de triglicerídios podem ter várias causas: como a dieta ou alterações relacionadas ao metabolismo lipídico. Este estudo foi composto por 96 indivíduos descendentes de japoneses residindo no Sul do Brasil (Cascavel-PR). O objetivo deste trabalho foi analisar alterações nos lipídios plasmáticos em uma população específica – indivíduos descendentes de japoneses residentes na região de Cascavel (PR) . Foram determinados os níveis de triglicerídios, colesterol total, HDL-colesterol, LDL-colesterol, VLDL-colesterol, apolipoproteína A-I e B e o padrão eletroforético de lipoproteínas em 96 indivíduos japoneses entre 10 a 89 anos. Para os níveis de triglicerídios, 18,7% dos indivíduos descendentes de japoneses obtiveram valores acima de 200 mg/dL.. Quando relacionamos os níveis de colesterol total, 69,7% dos indivíduos descendentes de japoneses possuem níveis acima da normalidade. Observamos dois padrões eletroforéticos de lipoproteínas na população japonesa; 10,4% desses indivíduos obtiveram alterações na banda pré-beta relacionada ao VLDL-colesterol e 8,3% obtiveram alterações nas bandas da origem (Quilomicra) e na banda pré-beta.

Terapia de reposição hormonal não altera a variabilidade da frequência cardíaca em mulheres pós-menopáusicas

INTRODUÇÃO. Mulheres pós-menopáusicas apresentam maior risco de desenvolvimento de doença arterial coronariana. Estudos observacionais demonstraram que a terapia de reposição hormonal produz efeitos benéficos no perfil lipídico e na modulação autonômica cardíaca. O aumento da variabilidade da freqüência cardíaca (VFC), até então atribuído à reposição hormonal, não foi testado em estudos randomizados, placebo-controlados, delineados para permitir a comparação entre as duas formas mais utilizadas de reposição hormonal. A VFC de 24 horas calculada pelo método não linear Mapa de Retorno Tridimensional permite avaliar tanto a modulação vagal como a simpática. OBJETIVOS Avaliar a modulação autonômica cardíaca de mulheres pósmenopáusicas através da análise da VFC no domínio do tempo e dos índices do Mapa de Retorno Tridimensional no ECG de 24 horas. Testar a hipótese de que a reposição hormonal contínua, seja com estradiol isolado (TRE), seja com estradiol associado à noretisterona (TRH), por um período de três meses, aumenta a VFC nessas mulheres. MÉTODOS Quarenta mulheres pós-menopáusicas (46 a 63 anos; média = 54,6 ± 4,2) foram randomizadas para um dos três tratamentos, de forma contínua: TRH, estrogenioterapia (TRE) ou placebo, por três meses consecutivos. Previamente, todas as mulheres foram submetidas a exames clínico, ginecológico e laboratorial (glicose, estradiol, HDL, LDL, triglicerídios; mamografia e ultrassonografia transvaginal). O ECG de 24 horas foi gravado em cada paciente, antes e após o tratamento, para calcular os índices da VFC. RESULTADOS Não houve diferença estatisticamente significativa entre os três grupos, após 3 meses de tratamento, nos índices da VFC e do Mapa de Retorno Tridimensional. A TRH diferiu da TRE apenas quanto ao perfil lipídico. A associação com a noretisterona provocou uma redução de 12,4 % no HDL (p = 0,008). CONCLUSÃO Em mulheres pós-menopáusicas, a terapia de reposição hormonal contínua com estradiol, ou com estradiol associado à noretisterona, por um período de 3 meses, não altera a modulação autonômica cardíaca avaliada pela VFC.

Efeito das prostaglandinas ciclopentenônicas sobre a expressão gênica do fator nuclear PPAR-γ, do receptor de scavenger CD36 e proteínas de apoptose em macrófagos : implicações para a fisiopatologia da aterosclerose

Considerando que as doenças cardiovasculares representam a maior causa de mortalidade e morbidade em países ocidentais, a aterosclerose se destaca pelo fato de predispor os pacientes ao infarto do miocárdio, a acidentes vasculares cerebrais e a doenças vasculares periféricas. Neste contexto, a oxidação de lipoproteínas do plasma, particularmente LDL, é um dos fatores de risco para eventos cardiovasculares, pois é reconhecida e internalizada por macrófagos, ocasionando a sua diferenciação em foam cells. Diversos fatores participam deste processo de diferenciação, como a expressão de receptores de scavenger CD 36, proporcionando aumento na captação de LDL oxidada, aumento na síntese endógena de colesterol e ativação de fatores nucleares que iniciam a transcrição de proteínas específicas e fatores de crescimento que disparam a aterogênese. Os fenômenos celulares relacionados à apoptose também são de especial importância, tanto no desenvolvimento da lesão aterosclerótica como na estabilidade da placa e formação de trombos. As prostaglandinas (PGs) ciclopentenônicas (CP-PGs), em particular a PGA2 e a 15-desóxi-∆12,14-PGJ2 são uma classe especial de PGs que, em diminutas concentrações, disparam a expressão das proteínas de choque térmico (hsp), que são citoprotetoras. Além disso, CP-PGs bloqueiam a ativação do fator nuclear pró-inflamatório NF-κB tornando-as potentes agentes antiinflamatórios. Embora as PGs das famílias A e J guardem uma série de características em comum, a 15-desóxi-∆12,14- PGJ2 é o ligante fisiológico do fator nuclear pró-aterogênico PPAR-γ, enquanto as PGs da família A ativam apenas a via citoprotetora das hsp. Este trabalho teve como objetivo avaliar os efeitos das CP-PGs sobre a expressão gênica de fatores relacionados à diferenciação de macrófagos em foam cells, bem como proteínas reguladoras do processo de apoptose, em células da linhagem pró-monocítica humana U937. Para tal, as células foram tratadas com CPPGs em presença e/ou ausência de LDL nat e LDL ox, o RNA foi extraído para a realização de RT-PCR para PPAR-γ, CD 36, HMG-CoA redutase e proteínas de apoptose Caspase 3, p53 e Bcl-xL. O tratamento estatístico utilizado foi análise de variância (ANOVA one-way) e teste “t” de student, com resultados expressos como médias + desvios-padrão da média, com P<0,05. Os resultados obtidos demontraram que as CP-PGs PGA2 (20µM-24h) e PGJ2 (1,5µM-24h) inibiram a expressão gênica do fator nuclear PPAR- γ (64 % (PGA2), 88 % (15- d-PGJ2)) nas células U937, em presença de LDL oxidada, quando comparado ao controle. PGA2 inibiu a expressão de HMG-CoA redutase (33 %), enzima chave da síntese de colesterol intracelular, e o tratamento com as CP-PGs também inibiu a apoptose nas células tratadas em presença de LDL oxidada. Os dados sugerem que as CP-PGs apresentam grande potencial para o tratamento da aterosclerose, já que, além de apresentarem efeito antiinflamatório, inibem a expressão do fator nuclear pró-aterogênico PPAR-γ, do receptor de scavenger CD36 (apenas a 15-desóxi-∆12,14-PGJ2) e da enzima HMG-CoA redutase. O bloqueio da apoptose nas células estudadas pode estar relacionado à citoproteção oferecida por estas PGs. Embora investigações in vivo deste laboratório tenham mostrado a eficácia do tratamento com CP-PGs em camundongos portadores de aterosclerose, estudos adicionais são necessários para esclarecer-se o efeito antiaterogênico das mesmas.