MARIA CECILIA GUSUKUMA

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FFM, Hospital das Clínicas, Faculdade de Medicina - Médico

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    DOWNREGULATION OF MONOCYTE ADHESION MOLECULES BY INHIBITION OF SYNTHESIS AND ABSORPTION OF CHOLESTEROL
    (2014) CERDA, A.; RODRIGUES, A. C.; ALVES, C.; GENVIGIR, F. D. V.; FAJARDO, C. M.; DOREA, E. L.; GUSUKUMA, M. C.; PINTO, G. A.; HIRATA, M. H.; HIRATA, R. D. C.
  • article 11 Citação(ões) na Scopus
    Modulation of Adhesion Molecules by Cholesterol-Lowering Therapy in Mononuclear Cells from Hypercholesterolemic Patients
    (2015) CERDA, Alvaro; RODRIGUES, Alice Cristina; ALVES, Camila; GENVIGIR, Fabiana Dalla Vecchia; FAJARDO, Cristina Moreno; DOREA, Egidio Lima; GUSUKUMA, Maria Cecilia; PINTO, Gelba Almeida; HIRATA, Mario Hiroyuki; HIRATA, Rosario Dominguez Crespo
    Introduction: Cholesterol-lowering therapy has been related with several pleiotropic effects including anti-inflammatory action in vascular endothelium; however, their influence on monocyte adhesion molecules is poorly described. Aims: To investigate the effect of inhibitors of synthesis (statins) and absorption (ezetimibe) of cholesterol on expression of adhesion molecules L-selectin, PSGL-1, VLA-4, LFA-1, and Mac-1 in mononuclear cells in vivo and in vitro using THP-1 cells. Methods: The influence of simvastatin (10 mg/day), ezetimibe (10 mg/day), and their combination (10 mg each/day) on mRNA expression of adhesion molecules was analyzed in peripheral blood mononuclear cells (PBMC) from hypercholesterolemics. The effects of atorvastatin, simvastatin, and ezetimibe on mRNA and protein expression of adhesion molecules were also evaluated in THP-1 cells. Results: Simvastatin/ezetimibe combination, but not the monotherapies, reduced the mRNA expression of the PSGL-1, LFA-1, and Mac-1 genes in PBMC from hypercholesterolemics. Total and LDL cholesterol in serum correlated with PSGL-1 mRNA expression, whereas HDL cholesterol negatively correlated with mRNA levels of L-selectin and VLA-4 genes (P < 0.05). Plasma hsCRP was also correlated with mRNA levels of VLA-4, LFA-1, and Mac-1 (P < 0.05). Atorvastatin and simvastatin at 10 mu M reduced mRNA and protein expression of L-selectin, PSGL-1, and VLA-4 in THP-1 cells (P < 0.05). Conclusion: Cholesterol-lowering therapy modulates gene expression of adhesion molecules in PBMC from hypercholesterolemics and THP-1 cells. Simvastatin/ezetimibe combination gives more benefits by reducing to a larger extent the expression of adhesion molecules in mononuclear cells.
  • article 20 Citação(ões) na Scopus
    Impact of 3 ' UTR genetic variants in PCSK9 and LDLR genes on plasma lipid traits and response to atorvastatin in Brazilian subjects: a pilot study
    (2015) ZAMBRANO, Tomas; HIRATA, Mario Hiroyuki; CERDA, Alvaro; DOREA, Egidio L.; PINTO, Gelba A.; GUSUKUMA, Maria C.; BERTOLAMI, Marcelo C.; SALAZAR, Luis A.; HIRATA, Rosario Dominguez Crespo
    Background: Hypercholesterolemia is a complex trait, resulting from a genetic interaction with lifestyle habits. Polymorphisms are a major source of genetic heterogeneity, and variations in 2 key cholesterol homeostasis genes; low-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type-9 (PCSK9), lead to dyslipidemia. So, we investigated the relation of 2 variants located in the 3'-UTR (3'-untranslated region) of LDLR (rs14158, G>A) and PCSK9 (rs17111557, C>T) with lipid profile and atorvastatin response. Methods: SNP influence on lipid profile was assessed in hypercholesterolemic patients (HC; n = 89) using atorvastatin (10 mg/day/4 weeks) and in normolipidemic subjects (NL; n = 171). Genotyping was completed through real-time PCR using TaqMan assays. Results: rs14158 G allele was higher in HC than in NL group (P = 0.043). NL subjects carrying the T allele of the PCSK9 variant had lower high-density lipoprotein cholesterol (HDL-c) than C allele carriers (P = 0.009). There was no association between LDLR and PCSK9 SNPs and atorvastatin response. Additionally, the PCSK9 variant creates a microRNA interaction site, which could implicate an epigenetic mechanism in PCSK9-dependent HDL-C regulation. Conclusions: The rs14158 SNP contributes to hypercholesterolemia. Also, a putative microRNA regulation may influence HDL-C variability observed in rs17111557 carriers. Cholesterol-lowering response to atorvastatin is not influenced by LDLR and PCSK9 variants.
  • article 6 Citação(ões) na Scopus
    Effects of short-term add-on ezetimibe to statin treatment on expression of adipokines and inflammatory markers in diabetic and dyslipidemic patients
    (2017) GUIMARAES, Elizandra Silva; CERDA, Alvaro; DOREA, Egidio Lima; BERNIK, Marcia Martins Silveira; GUSUKUMA, Maria Cecilia; PINTO, Gelba Almeida; FAJARDO, Cristina Moreno; HIRATA, Mario Hiroyuki; HIRATA, Rosario Dominguez Crespo
    AimThe influence of short-term add-on ezetimibe to simvastatin treatment on expression of adipokines and inflammatory markers was investigated in diabetic and nondiabetic patients with hypercholesterolemia. MethodHypercholesterolemic nondiabetic (HC, n=37) and diabetic (DM, n=47) patients were treated with simvastatin (SV, 10 or 20mg/d/8-wk) and then SV plus ezetimibe (SV+EZ, 10mg each/d/4wk). Serum lipids, glycemic profile, and inflammatory markers (hsCRP, adiponectin, resistin, VCAM-1, and ICAM-1) were evaluated before and after the add-on ezetimibe therapy. mRNA expression of ADIPOR1, ADIPOR2, RETN, VCAM1, and ICAM1 was measured by real-time PCR in peripheral blood mononuclear cells (PBMC). ResultsSerum concentrations of LDL and HDL cholesterol, and adiponectin were higher in HC than DM patients (P<.05). The add-on ezetimibe therapy reduced total and LDL cholesterol, apoB and adiponectin serum levels in HC and DM groups, and resistin in HC subjects (P<.05). DM patients showed higher expression of ADIPOR1, ADIPOR2, RETN, and VCAM1 in PBMC than subjects in HC group, before and after add-on ezetimibe therapy (P<.05). PBMC RETNmRNA expression was reduced by add-on ezetimibe therapy in HC individuals (P<.05), but not in DM subjects. ConclusionShort-term add-on ezetimibe to simvastatin treatment suppressing effects on hypercholesterolemia and adiponectinemia is independent of the diabetes status. Resistin serum levels and leukocyte mRNA expression are influenced by add-on ezetimibe to statin treatment.
  • bookPart
    Climatério e síndrome metabólica
    (2014) GUSUKUMA, Maria Cecília