EDNA REGINA NAKANDAKARE
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/10 - Laboratório de Lípides, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/10 - Laboratório de Lípides, Hospital das Clínicas, Faculdade de Medicina - Líder
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- The coronary artery calcium score is linked to plasma cholesterol synthesis and absorption markers: Brazilian Longitudinal Study of Adult Health(2020) NUNES, Valeria Sutti; BENSENOR, Isabela M.; LOTUFO, Paulo A.; PASSARELLI, Marisa; NAKANDAKARE, Edna Regina; QUINTAO, Eder Carlos RochaIt is controversial whether atherosclerosis is linked to increased intestinal cholesterol ab-sorption or synthesis in humans. The aim of the present study was to relate atherosclerosis to the measurements of plasma markers of cholesterol synthesis (desmosterol, lathosterol) and absorption (campesterol, sitosterol). In healthy male (n=344), non-obese, non-diabetics, belonging to the city of S ao Paulo branch of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we measured in plasma these non-cholesterol sterol markers, together with their anthropometric, dietary parameters, traditional atherosclerotic risk factors, and blood chemistry, coronary arterial calcium score (CAC), and ultrasonographically measured com-mon carotid artery intima-media thickness (CCA-IMT). Cases with CAC zero had the follow-ing parameters higher than cases with CAC = zero: age, waist circumference (WC), plasma total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and non-high density lipoprotein-cholesterol (non HDL-C). Plasma desmosterol and campesterol, duly corrected for TC, age, body mass index (BMI), waist circumference (WC), hypertension, smoking, and the homeostasis model assessment-insulin resistance (HOMA-IR) correlated with CAC, but not with CCA-IMT. The latter related to increased age, BMI, waist circumference (WC), and systolic blood pressure (SBP). Plasma HDL-C concentrations did not define CAC or CCA-IMT degrees, although in relation to the lower tertile of HDL-C in plasma the higher tertile of HDL-C had lower HOMA-IR and concentration of a cholesterol synthesis marker (desmosterol). Present work indicated that increased cholesterol synthesis and absorption represent primary causes of CAD, but not of the common carotid artery atherosclerosis.
- Screening of ABCG5 and ABCG8 Genes for Sitosterolemia in a Familial Hypercholesterolemia Cascade Screening Program(2022) TADA, Mauricio Teruo; ROCHA, Viviane Zorzanelli; LIMA, Isabella Ramos; OLIVEIRA, Theo Gremen Mimary; CHACRA, Ana Paula; MINAME, Marcio Hiroshi; NUNES, Valeria Sutti; NAKANDAKARE, Edna Regina; CASTELO, Maria Helane Costa Gurgel; JANNES, Cinthia Elim; SANTOS, Raul D.; KRIEGER, Jose Eduardo; PEREIRA, Alexandre CostaBackground: Sitosterolemia is a rare autosomal recessive disorder caused by homozygous or compound heterozygous variants in ABCG5/ABCG8. The disease is characterized by increased plasma plant sterols. Small case series suggest that patients with sitosterolemia have wide phenotypic heterogeneity with great variability on either plasma cholesterol levels or development of atherosclerotic cardiovascular disease. The present study aims to characterize the prevalence and clinical features of sitosterolemia participating in a familial hypercholesterolemia genetic cascade screening program. Methods: From 443 familial hypercholesterolemia index cases, 260 were negative for familial hypercholesterolemia genes and were sequenced for the ABCG5/8 genes. Clinical and laboratory characteristics of affected individuals were determined. Results: Eight (3.1%) index cases were found to be homozygous or compound heterozygous variant for ABCG5/ABCG8 genes, confirming the genetic diagnosis of sitosterolemia. Screening their relatives led to the identification of 6 additional confirmed sitosterolemia cases (3 homozygous and 3 compound heterozygous variant) and 18 carriers (heterozygous). The mean age of identified sitosterolemia cases (n=14) was 37.2 +/- 19.8 years, 50% were females, and 78.6% (all adults) presented either clinical or subclinical atherosclerotic cardiovascular disease. As expected, affected individuals presented elevated plasma plant sterol levels (mean beta-Sitosterol and campesterol, respectively, 160.3 +/- 107.1 and 32.0 +/- 19.6 mu g/mL) and the highest plasma LDL (low-density lipoprotein)-cholesterol was 269.0 +/- 120.0 mg/dL (range: 122-521 mg/dL). LDL-cholesterol mean reduction with therapy among cases was 65%. Eighty-three percent (83%) of identified sitosterolemia patients presented hematologic abnormalities. Conclusions: Testing genes associated with sitosterolemia in the molecular routine workflow of a familial hypercholesterolemia cascade screening program allowed the precise diagnosis of sitosterolemia in a substantial number of patients with varying LDL-C levels and high incidence of early atherosclerotic cardiovascular disease and hematologic abnormalities.
- 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.
- 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.
- The impact of dietary fatty acids on macrophage cholesterol homeostasis(2014) AFONSOA, Milessa da Silva; CASTILHO, Gabriela; LAVRADOR, Maria Silvia Ferrari; PASSARELLI, Marisa; NAKANDAKARE, Edna Regina; LOTTENBERG, Simao Augusto; LOTTENBERG, Ana MariaThe impact of dietary fatty acids in atherosclerosis development may be partially attributed to their effect on macrophage cholesterol homeostasis. This process is the result of interplay between cholesterol uptake and efflux, which are permeated by inflammation and oxidative stress. Although saturated fatty acids (SAFAs) do not influence cholesterol efflux, they trigger endoplasmic reticulum stress, which culminates in increased lectin-like oxidized LDL (oxLDL) receptor (LOX1) expression and, consequently, oxLDL uptake, leading to apoptosis. Unsaturated fatty acids prevent most SAFAs-mediated deleterious effects and are generally associated with reduced cholesterol efflux, although alpha-linolenic acid increases cholesterol export. Trans fatty acids increase macrophage cholesterol content by reducing ABCA-1 expression, leading to strong atherosclerotic plaque formation. As isomers of conjugated linoleic acid (CLAs) are strong PPAR gamma ligands, they induce cluster of differentiation (CD36) expression, increasing intracellular cholesterol content. Considering the multiple effects of fatty acids on intracellular signaling pathways, the purpose of this review is to address the role of dietary fat in several mechanisms that control macrophage lipid content, which can determine the fate of atherosclerotic lesions.
- The I405V and Taq1B polymorphisms of the CETP gene differentially affect sub-clinical carotid atherosclerosis(2012) PARRA, Eliane Soler; PANZOLDO, Natalia Baratella; KAPLAN, Denise; OLIVEIRA, Helena Coutinho Franco de; SANTOS, Jose Ernesto dos; CARVALHO, Luiz Sergio Fernandes de; SPOSITO, Andrei Carvalho; GIDLUND, Magnus; NAKAMURA, Ruy Tsutomu; ZAGO, Vanessa Helena de Souza; NAKANDAKARE, Edna Regina; QUINTAO, Eder Carlos Rocha; FARIA, Eliana Cotta deBackground: Cholesteryl ester transfer protein (CETP) plays a major role in lipid metabolism, but studies on the association of CETP polymorphisms with risks of cardiovascular disease are inconsistent. This study investigated whether the CETP gene I405V and Taq1B polymorphisms modified subclinical atherosclerosis in an asymptomatic Brazilian population sample. Methods: The polymorphisms were analyzed using polymerase chain reaction in 207 adult volunteers. Serum lipid profiles, oxLDL Ab titers, C-reactive protein and tumor necrosis factor-a concentrations and CETP and phospholipid transfer protein (PLTP) activities were determined, and common carotid artery intima-media thickness (cIMT) was measured using ultrasonography. Results: No differences in cIMT were observed between the presence or absence of the minor B2 and V alleles in either polymorphism. However, inverse correlations between mean cIMT and CETP activity in the presence of these polymorphisms were observed, and positive correlations of these polymorphisms with PLTP activity and oxLDL Ab titers were identified. Moreover, logistic multivariate analysis revealed that the presence of the B2 allele was associated with a 5.1-fold (CI 95%, OR: 1.26 - 21.06) increased risk for cIMT, which was equal and above the 66th percentile and positively interacted with age. However, no associations with the V allele or CETP and PLTP activities were observed. Conclusions: None of the studied parameters, including CETP activity, explained the different relationships between these polymorphisms and cIMT, suggesting that other non-determined factors were affected by the genotypes and related to carotid atherosclerotic disease.
bookPart Obesidade e metabolismo de lipídios(2015) NAKANDAKARE, Edna Regina; PASSARELLI, Marisa- Position Statement on Fat Consumption and Cardiovascular Health-2021(2021) IZAR, Maria Cristina de Oliveira; LOTTENBERG, Ana Maria; GIRALDEZ, Viviane Zorzanelli Rocha; SANTOS FILHO, Raul Dias dos; MACHADO, Roberta Marcondes; BERTOLAMI, Adriana; ASSAD, Marcelo Heitor Vieira; SARAIVA, Jose Francisco Kerr; FALUDI, Andre Arpad; MOREIRA, Annie Seixas Bello; GELONEZE, Bruno; MAGNONI, Carlos Daniel; SCHERR, Carlos; AMARAL, Cristiane Kovacs; ARAUJO, Daniel Branco de; CINTRA, Dennys Esper Correa; NAKANDAKARE, Edna Regina; FONSECA, Francisco Antonio Helfenstein; MOTA, Isabela Cardoso Pimentel; SANTOS, Jose Ernesto dos; KATO, Juliana Tieko; BEDA, Lis Mie Misuzawa; VIEIRA, Lis Proenca; BERTOLAMI, Marcelo Chiara; ROGERO, Marcelo Macedo; LAVRADOR, Maria Silvia Ferrari; NAKASATO, Miyoko; DAMASCENO, Nagila Raquel Teixeira; ALVES, Renato Jorge; SOARES, Lara Roberta; COSTA, Rosana Perim; MACHADO, Valeria Arruda
bookPart Dislipidemias(2017) PASSARELLI, Marisa; NAKANDAKARE, Edna Regina; QUINTãO, Eder Carlos RochabookPart Lipoproteína e aterogênese(2013) NAKANDAKARE, Edna Regina; PASSARELLI, Marisa