FERNANDA BUENO FUSCO
Projetos de Pesquisa
Unidades Organizacionais
LIM/10 - Laboratório de Lípides, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
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conferenceObject N-acetylcystein Reduces Lipid Peroxidation and Advanced Glycation Related to Prevention of Macrophage Endoplasmic Reticulum Stress Induced by Albumin Isolated from Rats With Chronic Kidney Disease(2014) MACHADO, Juliana T.; IBORRA, Rodrigo T.; FUSCO, Fernanda B.; CASTILHO, Gabriela; PINTO, Raphael S.; MACHADO-LIMA, Adriana; NAKANDAKARE, Edna R.; SHIMIZU, Maria Heloisa M.; SEGURO, Antonio Carlos; CATANOZI, Sergio; PASSARELLI, Marisa- 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.
conferenceObject CHROMATOGRAPHIC ANALYSIS OF THE LIPID FRACTIONS IN OBESE CLIENT-OWNED DOGS(2012) JERICO, M. M.; CHIQUITO, F. C.; FUSCO, F.; CATANOZI, S.; NUNES, V. S.; NAKANDAKARE, E. R.Obesity, a metabolic disease of multifactorial origin, impairs the health and longevity of individuals. Dyslipidemia, a common condition in obese animals, is usually associated to a variety of clinical problems, which include gastrointestinal alterations, hepatic lipidosis, atherosclerosis and metabolic syndrome. The aim of the study was to characterize the lipid profile and lipoprotein fractions in obese dogs (n=20) and compare them with control dogs (n=10), selected from a veterinary hospital environment. Lipoproteins (LP) were isolated by fast protein liquid chromatography (FPLC) system and plasma total cholesterol (TC) and triglycerides (TG) concentrations were measured by enzymatic methods. In control group, TC was 193±44 mg/dL (mean±SD) (percentage distribution among LP fractions: VLDL-C 2.34%, LDL-C 15.79%, HDL-C 81.86%); Plasma TG concentration was 50± 15 mg/dL (LP fraction percentage distribution: VLDL-TG 39.17%, LDL-TG 35.9%, HDL-TG 24.94%). In obese dogs, plasma TC was 227± 73 mg/dL (VLDL-C 3,325%, LDL-C21.64%, HDL-C 75.03%) whereas the TG values were 87.9 ± 52 mg/dL (VLDL-TG 61.98%, LDL-TG 24.71%, HDL-TG 13.36%). When compared to the normal dogs, the animals with obesity presented a significant increase (p<0.01) in plasmaTG and VLDL-TG levels as well as a lower HDL-TG concentration. There were not significant alterations in cholesterol fractions or TC between groups although they presented proportionally higher levels of TC, and LDL-C as well as lower HDL-C. It was concluded that obese dogs present a significant difference when compared to normal dogs in relation to triglyceride metabolism and their VLDL and HDL fractions, which has been previously shown in experimental model of obese canine insulin resistance. These findings suggest a higher risk of metabolic complications in obese client-owned dogs, like diabetes, hepatobiliary diseases and o f blood flow disturbances, like atherosclerosis.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.- N-acetylcysteine prevents endoplasmic reticulum stress elicited in macrophages by serum albumin drawn from chronic kidney disease rats and selectively affects lipid transporters, ABCA-1 and ABCG-1(2014) MACHADO, Juliana T.; IBORRA, Rodrigo T.; FUSCO, Fernanda B.; CASTILHO, Gabriela; PINTO, Raphael S.; MACHADO-LIMA, Adriana; NAKANDAKARE, Edna R.; SEGURO, Antonio C.; SHIMIZU, Maria H.; CATANOZI, Sergio; PASSARELLI, MarisaIn chronic kidney disease (CKD) nontraditional risk factors, such as oxidative stress and advanced glycation end products (AGE) contribute to cardiovascular disease. Particularly, disturbances in reverse cholesterol transport favor the development of atherosclerosis. We analyzed the influence of N-acetylcysteine (NAC) in CKD rats on plasma concentration of lipid peroxides (TBARS) and AGE and on the impact of serum albumin in the development of macrophage endoplasmic reticulum stress (ERS) and cholesterol efflux, namely apo A-I and HDL2-mediated cholesterol removal and ABCA-1 and ABCG-1 protein level. CKD was induced by 5/6 nephrectomy in 2-month old male Wistar rats. Controls (Sham) were false operated. Animals were treated or not with NAC (600 mg/L of water). After 60 days serum albumin was isolated by FPLC and purified by alcoholic extraction. J774 macrophages were incubated with serum albumin (1 mg/mL; 18 h) from all groups, and the expression of ERS markers (protein disulfide isomerase - PDI, Grp78 and Grp94), ABCA-1 and ABCG-1 determined by immunoblot. HDL2 or apo A-I were used for cholesterol efflux assays. Protein and lipid composition of total HDL from Sham and CKD was determined and these particles tested on their abilities to accept cell cholesterol. Comparisons were done by one-way ANOVA and Newman Keuls post test. After 60 days of CKD, body weight was 10% lower in CKD compared to Sham (p < 0.01). This was prevented by NAC. Urea, creatinine, total cholesterol (TC), triglycerides (TG) (mg/dL), proteinuria (mg/24 h) (Sham, n = 31; Sham + NAC, n = 20; CKD, n = 74; CKD + NAC, n = 32), total AGE and pentosidine (n = 8; fluorescence arbitrary unit) and TBARS (n = 7; nmoL/mL) were higher in CKD (122 +/- 8; 0.9 +/- 0.07; 151 +/- 6; 83 +/- 4; 46 +/- 2.5; 32,620 +/- 673; 16,700 +/- 1,370; 6.6 +/- 0.5, respectively) and in CKD + NAC (91.4 +/- 5; 0.6 +/- 0.02; 126 +/- 7.5; 73 +/- 6; 51 +/- 3.5; 24,720 +/- 1,114; 10,080 +/- 748; 4.5 +/- 0.5, respectively) in comparison to Sham (41 +/- 0.9; 0.4 +/- 0.03; 76 +/- 2.7; 51.5 +/- 3; 14 +/- 0.9; 21,750 +/- 960; 5,314 +/- 129; 2.0 +/- 0.2, respectively; p < 0.001) and Sham + NAC (40 +/- 0.9; 0.3 +/- 0.02; 76 +/- 2.6; 68 +/- 4; 18.4 +/- 1.5; 20,040 +/- 700; 5,050 +/- 267; 1.8 +/- 0.2, respectively; p < 0.001). TC, urea, creatinine, total AGE, pentosidine and TBARS were respectively, 17%, 25%, 33%, 24%, 40% and 28% (p < 0.01) lower in CKD + NAC, than in CKD. Glycemia was higher in Sham + NAC (107 +/- 4.6) and CKD + NAC (107 +/- 2.6) than in Sham (96 +/- 1.8; p < 0.05) and CKD (98 +/- 1.6; p < 0.01), respectively. In macrophages (n = 6), CKD albumin increased PDI (3 and 6 times, p < 0.01) and Grp94 (66% and 80%, p < 0.01) in comparison to Sham and CKD + NAC-albumin treated cells, respectively. ABCA-1 expression was lower (87% and 70%, p < 0.001) in macrophage treated with Sham + NAC and CKD albumin respectively in comparison to Sham albumin; ABCG-1 was higher (4 and 7 times, p < 0.001) in macrophages treated with Sham + NAC and CKD + NAC albumin, respectively in comparison to Sham and CKD albumin. Apo A-I mediated cholesterol efflux was lower (59% and 70%, p < 0.0001) in macrophage treated with Sham + NAC and CKD albumin respectively in comparison to Sham albumin, however, the HDL2 mediated cholesterol efflux was higher (54% and 25%, p < 0. 0001) in macrophage treated with Sham + NAC albumin, in comparison to Sham and CKD + NAC albumin, respectively. CKD-HDL was enriched in total protein and lipids compared to Sham-HDL but preserved its capacity to remove cholesterol from macrophages. NAC reduces plasma lipid peroxidation and AGE and abrogates ERS induced by CKD-albumin. Despite diminishing ABCA-1, NAC increases ABCG-1 that counteracts the reduction in apo A-I-mediated cholesterol efflux. NAC may contribute to attenuate the deleterious effects of CKD-albumin on lipid accumulation in macrophages helping to prevent atherogenesis in CKD.
- Glycated albumin induces lipid infiltration in mice aorta independently of DM and RAS local modulation by inducing lipid peroxidation and inflammation(2016) GOMES, Diego Juvenal; VELOSA, Ana Paula; OKUDA, Ligia Shimabukuro; FUSCO, Fernanda Bueno; SILVA, Karolinne Santana da; PINTO, Paula Ramos; NAKANDAKARE, Edna Regina; CORREA-GIANNELLA, Maria Lucia; WOODS, Tom; BRIMBLE, Margaret Anne; PICKFORD, Russell; RYE, Kerry-Anne; TEODORO, Walcy Rosolia; CATANOZI, Sergio; PASSARELLI, MarisaAims: Advanced glycated albumin (AGE-albumin) adversely impairs macrophage lipid homeostasis in vitro, which may be prevented by angiotensin receptor blockers. In vivo studies are inconclusive whether AGE-albumin itself plays important role in early-stage atherogenesis. We aimed at investigating how AGE-albumin by itself drives atherosclerosis development in dyslipidemic non-diabetic mice and if its effects are due to the activation of renin-angiotensin system in the arterial wall and the expression of genes and proteins involved in lipid flux. Methods and results: Murine albumin glycation was induced by incubation with 10 mM glycolaldehyde and C-albumin with PBS alone. Twelve-week-old-male apoE knockout mice were submitted to a daily IP injection of control (C) or AGE-albumin (2 mg/mL) during 30 days with or without losartan (LOS: 100 mg/L; C + LOS and AGE + LOS). Aortic arch was removed, and gene expression was determined by RT-PCR and protein content by immunofluorescence. Plasma lipid and glucose levels were similar among groups. Systolic blood pressure was similarly reduced in both groups treated with LOS. In comparison to C-albumin, aortic lipid infiltration was 5.3 times increased by AGE-albumin, which was avoided by LOS. LOS prevented the enhancement induced by AGE-albumin in Ager, Tnf and Cybb mRNA levels but did not reduce Olrl. Nfkb and Agt mRNA levels were unchanged by AGE-albumin. LOS similarly reduced Agtri a mRNA level in both C and AGE-albumin groups. In AGE-albumin-treated mice, immunofluorescence for carboxymethyl-lysine, 4-hydroxynonenal and RAGE was respectively, 4.8, 2.6 and 1.7 times enhanced in comparison to C-albumin. These increases were all avoided by LOS. Conclusions: AGE-albumin evokes a pre-stage of atherogenesis in dyslipidemic mice independently of the presence of diabetes mellitus or modulation in the RAS in part by the induction of lipid peroxidation and inflammation.