MARCIA KIYOMI KOIKE
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina
12 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 12
- Dietary interesterified fat enriched with palmitic acid induces atherosclerosis by impairing macrophage cholesterol efflux and eliciting inflammation(2016) AFONSO, Milessa Silva; LAVRADOR, Maria Silvia Ferrari; KOIKE, Marcia Kiyomi; CINTRA, Dennys Esper; FERREIRA, Fabiana Dias; NUNES, Valeria Sutti; CASTILHO, Gabriela; GIOIELLI, Luiz Antonio; BOMBO, Renata Paula; CATANOZI, Sergio; CALDINI, Elia Garcia; DAMACENO-RODRIGUES, Nilsa Regina; PASSARELLI, Marisa; NAKANDAKARE, Edna Regina; LOTTENBERG, Ana MariaInteresterified fats are currently being used to replace trans fatty acids. However, their impact on biological pathways involved in the atherosclerosis development was not investigated. Weaning male LDLr-KO mice were fed for 16 weeks on a high-fat diet (40% energy as fat) containing polyunsaturated (PUFA), TRANS, palmitic (PALM), palmitic interesterified (PALM INTER), stearic (STEAR) or stearic interesterified (STEAR INTER). Plasma lipids, lipoprotein profile, arterial lesion area, macrophage infiltration, collagen content and inflammatory response modulation were determined. Macrophage cholesterol efflux and the arterial expression of cholesterol uptake and efflux receptors were also performed. The interesterification process did not alter plasma lipid concentrations. Although PALM INTER did not increase plasma cholesterol concentration as much as TRANS, the cholesterol enrichment in the LDL particle was similar in both groups. Moreover, PALM INTER induced the highest IL-1 beta, MCP-1 and IL-6 secretion from peritoneal macrophages as compared to others. This inflammatory response elicited by PALM INTER was confirmed in arterial wall, as compared to PALM. These deleterious effects of PALM INTER culminate in higher atherosclerotic lesion, macrophage infiltration and collagen content than PALM, STEAR, STEAR INTER and PUFA. These events can partially be attributed to a macrophage cholesterol accumulation, promoted by apoAl and HDL2-mediated cholesterol efflux impairment and increased Olr-1 and decreased Abca1 and Nr1h3 expressions in the arterial wall. Interesterified fats containing palmitic acid induce atherosclerosis development by promoting cholesterol accumulation in LDL particles and macrophagic cells, activating the inflammatory process in LDLr-KO mice.
conferenceObject Palmitic Interesterified Fat Induces Atherosclerosis and Inflammatory Cytokine Secretion in LDL Receptor Knockout Mice(2014) AFONSO, Milessa S.; LAVRADOR, Maria Silvia F.; KOIKE, Marcia; BOMBO, Renata P.; NUNES, Valeria S.; CATANOZI, Sergio; CASTILHO, Gabriela; PASSARELLI, Marisa; NAKANDAKARE, Edna R.; LOTTENBERG, Ana Maria- Effect of echium oil combined with phytosterols on biomarkers of atherosclerosis in LDLr-knockout mice: Echium oil is a potential alternative to marine oils for use in functional foods(2015) BOTELHO, Patricia Borges; GUIMARAES, Jessica Pereira; MARIANO, Karina Rocha; AFONSO, Milessa da Silva; KOIKE, Marcia Kiyomi; LOTTENBERG, Ana Maria Pita; CASTRO, Inar AlvesBioactive compounds may be an alternative approach to prevent atherosclerosis. To evaluate this hypothesis, LDLr-knockout mice were supplemented with omega-3 fatty acids from Echium oil (10.24mg/d of oil with 1,14mg/d of SDA and 9.06mg/d of ALA) equivalent to 0.7mg/d of EPA after conversion, combined or not with phytosterols (0.76mg/d), during the first 2 months of life. Subsequently, dyslipidaemia was induced by a high-fat diet for the following 2 months. Echium oil, isolated or combined with phytosterols, improved lipid profile in plasma reducing triacylglycerol (90.37.6mg/dL) and VLDL-c (18.01.5mg/dL) concentrations when compared with Control (115.8 +/- 9.4mg/dL and 23.2 +/- 1.9mg/dL, respectively). Echium oil also increased catalase (5.66 +/- 0.13U/mg protein) while Echium oil combined with phytosterol increased glutathione peroxidase activity (26.27 +/- 0.10U/mg protein) when compared with Control (5.18 +/- 0.10U/mg protein and 25.31 +/- 0.16U/mg protein, respectively). In addition, groups receiving Echium oil have reduced malondialdehyde concentration in liver (p=0.05). However, no difference was observed in fatty streak lesions when compared with Control. Isolated phytosterols did not change cholesterol absorption and increased lesion area compared with control group. This result can be associated with the high dose applied in the first step of supplementation and with the form of supplementation (gavage). Practical applications: One factor that contributes to the number of deaths from cardiovascular disease is that pharmacological interventions usually start too late in life. For this reason, functional foods development is a very important strategy to prevent atherosclerosis, since their inclusion in diet can start much earlier. However, it represents a challenge because many physiological responses from chronic consumption of bioactive compounds are still unknown. In this study, considering the positive results on triglyceridemia and oxidative stress biomarkers, we suggest that Echium oil can be an alternative for development of functional foods. We selected Echium oil due to its higher proportion of stearidonic fatty acids (pro-EPA) and lower sensory limitation than marine oils. Echium oil improves lipid profile and reduces oxidative stress, while phytosterol increases fatty streak.
- Omega-6 polyunsaturated fatty acids prevent atherosclerosis development in LDLr-KO mice, in spite of displaying a pro-inflammatory profile similar to trans fatty acids (vol 224, pg 66, 2012)(2013) MACHADO, R. M.; NAKANDAKARE, E. R.; QUINTAO, E. C.; CAZITA, P. M.; KOIKE, M. K.; NUNES, V. S.; FERREIRA, F. D.; AFONSO, M. S.; BOMBO, R. P.; MACHADO-LIMA, A.; SORIANO, F. G.; CATANOZI, S.; LOTTENBERG, A. M.
- Omega-6 polyunsaturated fatty acids prevent atherosclerosis development in LDLr-KO mice, in spite of displaying a pro-inflammatory profile similar to trans fatty acids(2012) MACHADO, Roberta M.; NAKANDAKARE, Edna R.; QUINTAO, Eder C. R.; CAZITA, Patricia M.; KOIKE, Marcia K.; NUNES, Valeria S.; FERREIRA, Fabiana D.; AFONSO, Milessa S.; BOMBO, Renata P. A.; MACHADO-LIMA, Adriana; SORIANO, Francisco G.; CATANOZI, Sergio; LOTTENBERG, Ana MariaThe development of atherosclerosis and the inflammatory response were investigated in LDLr-KO mice on three high-fat diets (40% energy as fat) for 16 weeks: trans (TRANS), saturated (SAFA) or omega-6 polyunsaturated (PUFA) fats. The following parameters were measured: plasma lipids, aortic root total cholesterol (TC), lesion area (Oil Red-O), ABCA1 content and macrophage infiltration (immunohistochemistry), collagen content (Picrosirius-red) and co-localization of ABCA1 and macrophage (confocal microscopy) besides the plasma inflammatory markers (IL-6, TNF-alpha) and the macrophage inflammatory response to lipopolysaccharide from Escherichia coli (LPS). As expected, plasma TC and TG concentrations were lower on the PUFA diet than on TRANS or SAFA diets. Aortic intima macrophage infiltration, ABCA1 content, and lesion area on PUFA group were lower compared to TRANS and SAFA groups. Macrophages and ABCA1 markers did not co-localize in the atherosclerotic plaque, suggesting that different cell types were responsible for the ABCA1 expression in plaques. Compared to PUFA, TRANS and SAFA presented higher collagen content and necrotic cores in atherosclerotic plaques. In the artery wall, TC was lower on PUFA compared to TRANS group; free cholesterol was lower on PUFA compared to TRANS and SAFA; cholesteryl ester concentration did not vary amongst the groups. Plasma TNF-alpha concentration on PUFA and TRANS-fed mice was higher compared to SAFA. No difference was observed in IL-6 concentration amongst groups. Regarding the macrophage inflammatory response to LPS, TRANS and PUFA presented higher culture medium concentrations of IL-6 and TNF-alpha as compared to SAFA. The PUFA group showed the lowest amount of the anti-inflammatory marker IL-10 compared to TRANS and SAFA groups. In conclusion, PUFA intake prevented atherogenesis, even in a pro-inflammatory condition.
- Dietary phytosterol does not accumulate in the arterial wall and prevents atherosclerosis of LDLr-KO mice(2013) BOMBO, Renata P. A.; AFONSO, Milessa S.; MACHADO, Roberta M.; LAVRADOR, Maria Silvia Ferrari; NUNES, Valeria S.; QUINTAO, Eder R.; KOIKE, Marcia; CATANOZI, Sergio; LIN, Chin Jia; NAKANDAKARE, Edna R.; LOTTENBERG, Ana MariaScope: There have been conflicting reports on the usefulness of phytosterols (PS) in preventing atherosclerosis. We evaluated the effects of dietary PS supplementation in LDLr-KO male mice on the plasma and aorta sterol concentrations and on atherosclerotic lesion development. Methods and results: Mice were fed a high fat diet (40% of energy) supplemented with or without PS (2% w/w, n = 10). Plasma and arterial wall cholesterol and PS concentrations, lesion area, macrophage infiltration, and mRNA expression from LOX-1, CD36, ABCA1 and ABCG1 in peritoneal macrophages were measured. After 16 weeks, the plasma cholesterol concentration in PS mice was lower than that in the controls (p = 0.02) and in the arterial wall (p = 0.03). Plasma PS concentrations were higher in PS-fed animals than in controls (p < 0.0001); however, the arterial wall PS concentration did not differ between groups. The atherosclerotic lesion area in the PS group (n = 5) was smaller than that in controls (p = 0.0062) and the macrophage area (p = 0.0007). PS correlates negatively with arterial lipid content and macrophage (r = -0.76; p < 0.05). PS supplementation induced lower ABCG1 mRNA expression (p < 0.05). Conclusions: Despite inducing an increase in PS plasma concentration, PS supplementation is not associated with its accumulation in the arterial wall and prevents atherosclerotic lesion development.
- Flaxseed oil rich in omega-3 protects aorta against inflammation and endoplasmic reticulum stress partially mediated by GPR120 receptor in obese, diabetic and dyslipidemic mice models(2018) MOURA-ASSIS, Alexandre; AFONSO, Milessa Silva; OLIVEIRA, Vanessa de; MORARI, Joseane; SANTOS, Gustavo Aparecido dos; KOIKE, Marcia; LOTTENBERG, Ana Maria; CATHARINO, Rodrigo Ramos; VELLOSO, Licio Augusto; SILVA, Adelino Sanchez Ramos da; MOURA, L. P. de; ROPELLE, Eduardo Rochete; PAULI, Jose Rodrigo; CINTRA, Dennys Esper CorreaThe ""first hit"" to atherogenesis is driven by toll-like receptor 4, endoplasmic reticulum stress and ultimately metabolic dysfunction. In this study, we hypothesized that a flaxseed oil-enriched diet (FS) abolishes these inflammatory signaling pathway and restore metabolic homeostasis by activating the fatty acid receptor GPR120 in aorta of obese mice. Glucose homeostasis was assessed by GTT and ITT; lipidomics was performed using a Hybrid Ion Trap-Orbitrap Mass Spectrometer; serum lipids were measured using colorimetric assays; GPR120 and infiltrating macrophages were analyzed by immunofluorescence; protein immunoprecipitation and gene expression were evaluated by Western blot and RT-PCR, respectively. There were no differences in body weight and food intake between the groups from both strains (Swiss and LDLr-KO mice). Gil and cholesterol levels were improved by FS in both mice models. Lipidomics showed an increase in omega 3 (C18:3) content, meanwhile stearic acid (C18:0) was not detected in endothelial tissue in response to FS. Moreover, FS markedly decreased pro inflammatory (IL-1 beta, TNF-alpha, pI kappa B alpha, pIKK beta) and unfolded protein response markers (ATF6 and GRP78) in aorta. In Swiss mice, GPR120 was partially involved in the omega 3-mediated anti-inflammatory actions, disrupting TLR4 pathway, but not in LDLr-KO mice. Partial replacement of dietary saturated by unsaturated omega 3 fatty acids contributes to inhibition of cardiovascular risk markers, pro-inflammatory cytokines and ER stress sensors and effectors in the aorta. However, downregulation of inflammation is not mediated by arterial GPR120 activation.
- Interesterified Fats Induce Deleterious Effects on Adipose Tissue and Liver in LDLr-KO Mice(2019) LAVRADOR, Maria Silvia Ferrari; AFONSO, Milessa Silva; CINTRA, Dennys Esper; KOIKE, Marcia; NUNES, Valeria Sutti; DEMASI, Marina; LIN, Chin Jia; BEDA, Lis Mie Masuzawa; GIOIELLI, Luiz Antonio; BOMBO, Renata de Paula Assis; MACHADO, Roberta Marcondes; CATANOZI, Sergio; NAKANDAKARE, Edna Regina; LOTTENBERG, Ana MariaInteresterified fats are being widely used by the food industry in an attempt to replace trans fatty acids. The effect of interesterified fats containing palmitic or stearic acids on lipid metabolism and inflammatory signaling pathways in adipose and hepatic tissues was evaluated. Male LDLr-KO mice were fed a high-fat diet containing polyunsaturated (PUFA), palmitic (PALM), palmitic interesterified (PALM INTER), stearic (STEAR), or stearic interesterified (STEAR INTER) fats for 16 weeks. The expression of genes and protein levels involved in lipid metabolism and inflammatory processes in liver and white adipose tissue was determined by quantitative RT-PCR and by Western blot, respectively. The infiltration of inflammatory cells in hepatic and adipose tissues was determined by eosin and hematoxylin, while liver collagen content was determined by Sirius Red staining. Both interesterified fats increased liver collagen content and JNK phosphorylation. Additionally, the STEAR INTER group developed nonalcoholic steatohepatitis (NASH) associated with higher neutrophil infiltration. PALM INTER induced adipose tissue expansion and enlargement of adipocytes. Furthermore, PALM INTER triggered increased IKK phosphorylation and TNF protein content, conditions associated with the upstream activation of the NFkB signaling pathway. STEAR INTER induced NASH, while PALM INTER triggered hepatic fibrosis and adipocyte hypertrophy with inflammatory response in LDLr-KO mice.
- Dietary interesterified fat enriched with palmitic acid induces atherosclerosis by impairing macrophage cholesterol efflux and eliciting inflammation (vol 32C, pg 91, 2016)(2016) AFONSO, Milessa Silva; LAVRADOR, Maria Silvia Ferrari; KOIKE, Marcia Kiyomi; CINTRA, Dennys Esper; FERREIRA, Fabiana Dias; NUNES, Valeria Sutti; CASTILHO, Gabriela; GIOIELLI, Luiz Antonio; BOMBO, Renata Paula; CATANOZI, Sergio; CALDINI, Elia Garcia; DAMACENO-RODRIGUES, Nilsa Regina; PASSARELLI, Marisa; NAKANDAKARE, Edna Regina; LOTTENBERG, Ana Maria
conferenceObject Interesterified Fats Induce Nonalcoholic Steatohepatitis or Enhance the Adipose Tissue and Adipocyte Hypertrophy(2014) LAVRADOR, Maria Silvia F.; AFONSO, Milessa S.; KOIKE, Marcia; BOMBO, Renata P.; CINTRA, Dennys E.; NUNES, Valeria S.; CATANOZI, Sergio; NAKANDAKARE, Edna R.; LOTTENBERG, Ana Maria