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
3 resultados
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- 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.
- 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.
- 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