GUILHERME DA SILVA FERREIRA
Projetos de Pesquisa
Unidades Organizacionais
FFM, Hospital das Clínicas, Faculdade de Medicina
LIM/10 - Laboratório de Lípides, Hospital das Clínicas, Faculdade de Medicina
LIM/10 - Laboratório de Lípides, Hospital das Clínicas, Faculdade de Medicina
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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.- Cholesterol metabolism in aging simultaneously altered in liver and nervous system(2022) NUNES, Valeria Sutti; FERREIRA, Guilherme da Silva; QUINTAO, Eder Carlos RochaIn humans, aging, triggers increased plasma concentrations of triglycerides, cholesterol, low-density lipoproteins and lower capacity of high-density lipoproteins to remove cellular cholesterol. Studies in rodents showed that aging led to cholesterol accumulation in the liver and decrease in the brain with reduced cholesterol synthesis and increased levels of cholesterol 24-hydroxylase, an enzyme responsible for removing cholesterol from the brain. Liver diseases are also related to brain aging, inducing changes in cholesterol metabolism in the brain and liver of rats. It has been suggested that late onset Alzheimer's disease is associated with metabolic syndrome. Non-alcoholic fatty liver is associated with lower total brain volume in the Framingham Heart Study offspring cohort study. Furthermore, disorders of cholesterol homeostasis in the adult brain are associated with neurological diseases such as Niemann-Pick, Alzheimer, Parkinson, Huntington and epilepsy. Apolipoprotein E (apoE) is important in transporting cholesterol from astrocytes to neurons in the etiology of sporadic Alzheimer's disease, an aging-related dementia. Desmosterol and 24S-hydroxycholesterol are reduced in ApoE KO hypercholesterolemic mice. ApoE KO mice have synaptic loss, cognitive dysfunction, and elevated plasma lipid levels that can affect brain function. In contrast to cholesterol itself, there is a continuous uptake of 27hydroxycholesterol in the brain as it crosses the blood-brain barrier and this flow can be an important link between intra-and extracerebral cholesterol homeostasis. Not surprisingly, changes in cholesterol metabolism occur simultaneously in the liver and nervous tissues and may be considered possible biomarkers of the liver and nervous system aging.
- The Plasma Distribution of Non-cholesterol Sterol Precursors and Products of Cholesterol Synthesis and Phytosterols Depend on HDL Concentration(2022) NUNES, Valeria Sutti; SILVA, Eliton Juniro da; FERREIRA, Guilherme da Silva; ASSIS, Sayonara Ivana Santos de; CAZITA, Patricia Miralda; NAKANDAKARE, Edna Regina; ZAGO, Vanessa Helena de Souza; FARIA, Eliana Cotta de; QUINTAO, Eder Carlos RochaNon-cholesterol sterols are transported in plasma lipoproteins and are consequently important in cholesterol metabolism. We investigated the distribution of non-cholesterol sterol precursors of cholesterol synthesis (NCSPCS), oxysterols, and phytosterols in lipoproteins of healthy subjects differing according to HDL-Cholesterol (HDL-C) plasma levels. Elevated NCSPCS (desmosterol, lathosterol) in the High HDL group suggests that HDL exports these sterols from cells, but not the cholesterol metabolite 24-OHC which was higher in the Low HDL group than in the High HDL group. 27-hydroxycholesterol (27OH-C) plasma levels did not differ between groups. Percentage of NCSPCS and phytosterols predominates in LDL, but did not differ between groups. Thirty percent of desmosterol and lathosterol are present in HDL, with the High HDL group carrying higher percentage of these sterols. A high percentage of campesterol and sitosterol in HDL suggests that phytosterols are absorbed by enterocytes, and that HDL could be a marker of the ABCA1/ApoA1 intestinal activity.
- Plasma lathosterol measures rates of cholesterol synthesis and efficiency of dietary phytosterols in reducing the plasma cholesterol concentration(2022) NUNES, Valeria Sutti; ILHA, Angela de Oliveira Godoy; FERREIRA, Guilherme da Silva; BOMBO, Renata de Paula Assis; AFONSO, Milessa Silva; LAVRADOR, Maria Silvia Ferrari; MACHADO, Roberta Marcondes; NAKANDAKARE, Edna Regina; QUINTA, Eder Carlos Rocha; LOTTENBERG, Ana MariaObjectives: Because the plasma campesterol/cholesterol ratio does not differ between groups that absorb different amounts of cholesterol, the authors investigated whether the plasma Phytosterols (PS) relate to the body's cholesterol synthesis rate measured as non-cholesterol sterol precursors (lathosterol). Method: The authors studied 38 non-obese volunteers (58 +/- 12 years; Low-Density Lipoprotein Cholesterol - LDLC >= 130 mg/dL) randomly assigned to consume 400 mL/day of soy milk (Control phase) or soy milk + PS (1.6 g/ day) for four weeks in a double-blind, cross-over study. PS and lathosterol were measured in plasma by gas chromatography coupled to mass spectrophotometry. Results: PS treatment reduced plasma total cholesterol concentration (-5.5%, p < 0.001), LDL-C (-7.6%, p < 0.001), triglycerides (-13.6%, p < 0.0085), and apolipoprotein B (apo B) (-6.3%, p < 0.008), without changing high density lipoprotein cholesterol (HDL-C concentration), but plasma lathosterol, campesterol and sitosterol expressed per plasma cholesterol increased. Conclusions: The lathosterol-to-cholesterol plasma ratio predicted the plasma cholesterol response to PS feeding. The highest plasma lathosterol concentration during the control phase was associated with a lack of response of plasma cholesterol during the PS treatment period. Consequently, cholesterol synthesis in non-responders to dietary PS being elevated in the control phase indicates these cases resist to further synthesis rise, whereas responders to dietary PS, having in the control phase synthesis values lower than non-responders, expand synthesis on alimentary PS. Responders absorb more PS than non-responders, likely resulting from responders delivering into the intestinal lumen less endogenous cholesterol than non-responders do, thus facilitating greater intestinal absorption of PS shown as increased plasma PS concentration.
- Phytosterols Supplementation Reduces Endothelin-1 Plasma Concentration in Moderately Hypercholesterolemic Individuals Independently of Their Cholesterol-Lowering Properties(2020) ILHA, Angela Oliveira Godoy; NUNES, Valeria Sutti; AFONSO, Milessa Silva; NAKANDAKARE, Edna Regina; FERREIRA, Guilherme da Silva; BOMBO, Renata de Paula Assis; GIORGI, Ricardo Rodrigues; MACHADO, Roberta Marcondes; QUINTAO, Eder Carlos Rocha; LOTTENBERG, Ana MariaExperimental and clinical studies have demonstrated the effect of phytosterols (PS) on reducing plasma levels of cholesterol and LDL-c, but the effects of plant sterols beyond cholesterol-lowering are still questionable. Since inflammation and endothelial dysfunction are involved in the pathogenesis of atherosclerosis, this study aims to evaluate the effect of PS on biomarkers involved in atherosclerosis progression and whether these effects are independent of alterations in plasma LDL-c levels. Thirty-eight moderately hypercholesterolemic volunteers (58 +/- 12 years; LDL-c >= 130 mg/dL) were randomly assigned to consume 400 mL/day of soy milk or soy milk + PS (1.6 g/day) for 4 weeks in a double-blind, placebo-controlled, cross-over study. Blood samples were collected and lipid profiles and biomarkers for inflammation and endothelial dysfunction determined. The results showed that PS treatment reduced endothelin-1 plasma concentration by 11% (p = 0.02) independently of variations in plasma levels of LDL-c. No alterations were observed regarding fibrinogen, IL-6, hs-CRP, SAA, TNF alpha, or VCAM-1 between placebo and PS-treated groups. Furthermore, PS reduced total plasma cholesterol concentration (-5,5%, p < 0.001), LDL-c (-6.4%, p < 0.05), triglycerides (-8.3%, p < 0.05), and apo B (-5.3%, p < 0.05), without changing HDL-c concentration (p > 0.05). Therefore, PS supplementation effectively lowers endothelin-1 independently of the reductions in plasma levels of LDL-c, contributing to the comprehension of the effect of plant sterols on endothelial function and prevention of cardiovascular diseases.