EDER CARLOS ROCHA QUINTAO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/10 - Laboratório de Lípides, Hospital das Clínicas, Faculdade de Medicina
LIM/10 - Laboratório de Lípides, Hospital das Clínicas, Faculdade de Medicina
11 resultados
Resultados de Busca
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- Cholesterol metabolism in mice models of genetic hypercholesterolemia(2020) NUNES, Valeria S.; CAZITA, Patricia M.; CATANOZI, Sergio; NAKANDAKARE, Edna R.; QUINTAO, Eder C. R.Monogenic familial hypercholesterolemia is characterized by impaired cellular uptake of apolipoprotein B containing lipoproteins. However, its consequences on whole-body cholesterol metabolism are unclear. We investigated cholesterol metabolism in wild-type mice (control) and in knockout (KO) mice for the low-density lipoprotein receptor (LDLR-KO) and for apolipoprotein E (apoE-KO) containing the genetic basis of the C57BL/6J mice, under a cholesterol-free diet. Cholesterol and ""non-cholesterol"" sterols (cholestanol, desmosterol, and lathosterol) were measured in plasma, tissues, as well as in feces as cholesterol and its bacterial modified products (neutral sterols) using gas chromatography/mass spectrometry, and bile acids were measured by an enzymatic method. Compared to controls, LDLR-KO mice have elevated plasma and whole-body cholesterol concentrations, but total fecal sterols are not modified, characterizing unaltered body cholesterol synthesis together with impaired body cholesterol excretion. ApoE-KO mice presented the highest concentrations of plasma cholesterol, whole-body cholesterol, cholestanol, total fecal sterols, and cholestanol, compatible with high cholesterol synthesis rate; the latter seems attributed to elevated body desmosterol (Bloch cholesterol synthesis pathway). Nonetheless, whole-body lathosterol (Kandutsch-Russel cholesterol synthesis pathway) decreased in both KO models, likely explaining the diminished fecal bile acids. We have demonstrated for the first time quantitative changes of cholesterol metabolism in experimental mouse models that explain differences between LDLR-KO and apoE-KO mice. These findings contribute to elucidate the metabolism of cholesterol in human hypercholesterolemia of genetic origin.
- Phytosterol containing diet increases plasma and whole body concentration of phytosterols in apoE-KO but not in LDLR-KO mice(2019) NUNES, Valeria Sutti; CAZITA, Patricia Miralda; CATANOZI, Sergio; NAKANDAKARE, Edna Regina; QUINTAO, Eder Carlos RochaPhytosterol metabolism is unknown in the hypercholesterolemia of genetic origin. We investigated the metabolism of phytosterols in a cholesterol-free, phytosterol-containing standard diet in hypercholesterolemic mice knockouts for low density lipoprotein receptor (LDLR) and apolipoprotein E (apoE) mice compared to wild-type mice (controls). Phytosterols were measured in mice tissues by GCMS. ApoE-KO mice absorbed less phytosterols than LDLR-KO and the latter absorbed less phytosterols than control mice, because the intestinal campesterol content was low in both KO mice, and sitosterol was low in the intestine in apoE-KO mice as compared to LDLR-KO mice. Although the diet contained nine times more sitosterol than campesterol, the concentration of sitosterol was lower than that of campesterol in plasma in LDLR-KO, and in the liver in controls and in LDLR-KO, but only in apoE-KO. On the other hand, in the intestine sitosterol was higher than campesterol in controls, and in LDLR-KO but with a tendency only in apoE-KO. Because of the high dietary supply of sitosterol, sitosterol was better taken up by the intestine than campesterol, but the amount of sitosterol was lower than that of campesterol in the liver, while in the whole body the amounts of these phytosterols do not differ from each other. Therefore, via intestinal lymph less sitosterol than campesterol was transferred to the body. However, as compared to controls, in apoE-KO mice, but not in LDLR-KO mice, the increase in campesterol and sitosterol in plasma and in the whole body indicating that apoE-KO mice have a marked defect in the elimination of both phytosterols from the body.
conferenceObject LIPOPROTEINS AND LIPID METABOLISM: HDL. AEROBIC EXERCISE TRAINING DOES NOT SYSTEMATICALLY AFFECT MACROPHAGE GENE EXPRESSION INVOLVED IN REVERSE CHOLESTEROL TRANSPORT AND CHOLESTEROL EFFLUX IN CETP TRANSGENIC MICE(2016) PINTO, P. R.; SILVA, K. S.; GOMES, D. J.; MACHADO-LIMA, A.; IBORRA, R. T.; FERREIRA, G. S.; QUINTAO, E. C. R.; NAKANDAKARE, E. R.; MACHADO, U. F.; CORREA-GIANNELLA, M. L. C.; CATANOZI, S.; PASSARELLI, M.conferenceObject CHOLESTEROL CONTENT AND SYNTHESIS IN THE BRAIN OF APOE KNOCKOUT MICE(2018) NUNES, V. Sutti; CAZITA, P. Miralda; CATANOZI, S.; NAKANDAKARE, E. R.; QUINTAO, E. C. R.- 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.
- Low-sodium diet induces atherogenesis regardless of lowering blood pressure in hypertensive hyperlipidemic mice(2017) FUSCO, Fernanda B.; GOMES, Diego J.; BISPO, Kely C. S.; TOLEDO, Veronica P.; BARBEIRO, Denise F.; CAPELOZZI, Vera L.; FURUKAWA, Luzia N. S.; VELOSA, Ana P. P.; TEODORO, Walcy R.; HEIMANN, Joel C.; QUINTAO, Eder C. R.; PASSARELLI, Marisa; NAKANDAKARE, Edna R.; CATANOZI, SergioThis study investigated the influence of sodium restriction and antihypertensive drugs on atherogenesis utilizing hypertensive (H) low-density lipoprotein-receptor knockout mice treated or not with losartan (Los) or hydralazine (Hyd) and fed low-sodium (LS) or normal-sodium (NS) chow. Despite reducing the blood pressure (BP) of H-LS mice, the LS diet caused arterial lipid infiltration due to increased plasma total cholesterol (TC) and triglycerides (TG). Los and Hyd reduced the BP of H-LS mice, and Los effectively prevented arterial injury, likely by reducing plasma TG and nonesterified fatty acids. Aortic lipid infiltration was lower in Los-treated H-LS mice (H-LS+Los) than in normotensive (N)-LS and H-LS mice. Aortic angiotensin II type 1 (AT1) receptor content was greater in H-NS than H-LS mice and in H-LS+Hyd than H-LS+Los mice. Carboxymethyl-lysine (CML) and receptor for advanced glycation end products (RAGE) immunostaining was greater in H-LS than H-NS mice. CML and RAGE levels were lower in LS animals treated with antihypertensive drugs, and Hyd enhanced the AT1 receptor level. Hyd also increased the gene expression of F4/80 but not tumor necrosis factor-a, interleukin (IL)-1 beta, IL-6, IL-10, intercellular adhesion molecule-1 or cluster of differentiation 66. The novelty of the current study is that in a murine model of simultaneous hypertension and hyperlipidemia, the pleiotropic effect of chronic, severe sodium restriction elicited aortic damage even with reduced BP. These negative effects on the arterial wall were reduced by AT1 receptor antagonism, demonstrating the influence of angiotensin II in atherogenesis induced by a severely LS diet.
- 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.
- Aerobic Exercise Improves Reverse Cholesterol Transport in Cholesteryl Ester Transfer Protein Transgenic Mice(2011) ROCCO, D. D. F. M.; OKUDA, L. S.; PINTO, R. S.; FERREIRA, F. D.; KUBO, S. K.; NAKANDAKARE, E. R.; QUINTAO, E. C. R.; CATANOZI, S.; PASSARELLI, M.We analyzed the effect of a 6-week aerobic exercise training program on the in vivo macrophage reverse cholesterol transport (RCT) in human cholesteryl ester transfer protein (CETP) transgenic (CETP-tg) mice. Male CETP-tg mice were randomly assigned to a sedentary group or a carefully supervised exercise training group (treadmill 15 m/min, 30 min sessions, five sessions per week). The levels of plasma lipids were determined by enzymatic methods, and the lipoprotein profile was determined by fast protein liquid chromatography (FPLC). CETP activity was determined by measuring the transfer rate of (14)C-cholesterol from HDL to apo-B containing lipoproteins, using plasma from CETP-tg mice as a source of CETP. The reverse cholesterol transport was determined in vivo by measuring the [(3)H]-cholesterol recovery in plasma and feces (24 and 48 h) and in the liver (48 h) following a peritoneal injection of [(3)H]-cholesterol labeled J774-macrophages into both sedentary and exercise trained mice. The protein levels of liver receptors were determined by immunoblot, and the mRNA levels for liver enzymes were measured using RT-PCR. Exercise training did not significantly affect the levels of plasma lipids or CETP activity. The HDL fraction assessed by FPLC was higher in exercise-trained compared to sedentary mice. In comparison to the sedentary group, a greater recovery of [(3)H]-cholesterol from the injected macrophages was found in the plasma, liver and feces of exercise-trained animals. The latter occurred even with a reduction in the liver CYP7A1 mRNA level in exercised trained animals. Exercise training increased the liver LDL receptor and ABCA-1 protein levels, although the SR-BI protein content was unchanged. The RCT benefit in CETP-tg mice elicited by exercise training helps to elucidate the role of exercise in the prevention of atherosclerosis in humans.
conferenceObject LOW-SALT DIET INDUCES ATHEROSCLEROSIS INDEPENDENT OF LOWERING BLOOD PRESSURE IN HYPERTENSIVE MICE(2016) CATANOZI, S.; FUSCO, F.; GOMES, D.; BISPO, K.; TOLEDO, V.; BARBEIRO, D.; CAPELOZZI, V.; FURUKAWA, L.; VELOSA, A. P.; TEODORO, W.; HEIMANN, J.; QUINTAO, E.; PASSARELLI, M.; NAKANDAKARE, E.