Nucleo de Pos Graduacao e Pesquisa

Belo Horizonte, Brazil

Nucleo de Pos Graduacao e Pesquisa

Belo Horizonte, Brazil
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Andrade V.L.,Nucleo de Pos Graduacao e Pesquisa | Petruceli E.,Nucleo de Pos Graduacao e Pesquisa | Belo V.A.,University of Sao Paulo | Andrade-Fernandes C.M.,Santa Casa de Belo Horizonte | And 4 more authors.
Clinical Biochemistry | Year: 2012

Objectives: To compare the plasma concentrations of matrix metalloproteinase (MMP)-9, tissue inhibitor of MMP (TIMP)-1, MMP-8, and myeloperoxidase (MPO) for obese and lean women. Design and methods: We recruited 30 lean and 36 obese women without comorbidities. The MMP-9, TIMP-1, and MMP-8 levels were measured using enzyme-linked immunosorbent assay (ELISA). MPO activity was assessed by a colorimetric assay. Results: Obese women had higher MMP-9 levels and MMP-9:TIMP-1 ratios than lean women. Conversely, the MMP-8 levels and MMP-8:TIMP-1 ratios in the obese women were significantly lower than those in the lean women despite neutrophil activation, which was assessed by MPO activity. Conclusion: We observed that MMP-9 and MMP-8 had distinct profiles, which suggested that these 2 enzymes play different roles in obesity. © 2012 The Canadian Society of Clinical Chemists.


Luizon M.R.,University of Sao Paulo | Palei A.C.T.,University of Campinas | Sandrim V.C.,Nucleo de Pos Graduacao e Pesquisa
Journal of Pregnancy | Year: 2012

Valenzuela and colleagues have recently reviewed some polymorphisms in important candidate genes involved in different pathogenic mechanisms related to preeclampsia (PE) and concluded that various studies in different populations have identified maternal polymorphisms associated with PE. However, we would like to contribute to some studies regarding candidate genes related to angiogenesis and endothelial dysfunction in PE performed in the Brazilian population. Specifically, genotypes and haplotypes formed by polymorphisms of VEGF, eNOS and MMP-9, along with an example of the interaction among these genes in the prediction of PE. Our suggestions may provide additional information with clinical relevance to PE susceptibility. © 2012 Marcelo Rizzatti Luizon et al.


Eleuterio N.M.,Nucleo de Pos Graduacao e Pesquisa | Palei A.C.T.,University of Campinas | Rangel Machado J.S.,University of Sao Paulo | Tanus-Santos J.E.,University of Sao Paulo | And 2 more authors.
Clinica Chimica Acta | Year: 2013

Background: Controversial results have been reported regarding plasma adiponectin levels in preeclampsia (PE) compared to healthy pregnancies (HP). Adiponectin activates eNOS, increasing the levels of the vasodilator nitric oxide (NO). PE reduces the levels of nitrite (an NO marker) and induces higher levels of ADMA (an endogenous eNOS inhibitor) compared to HP. No previous study has examined whether a positive correlation exists between adiponectin and nitrite in HP and PE and how ADMA may interfere with this correlation. Methods: We measured plasma nitrite concentrations using an ozone-based chemiluminescence assay, and plasma ADMA and adiponectin levels using enzyme immunoassays in 117 pregnant women (70 healthy and 47 preeclamptic). Results: We found higher adiponectin levels (23.6. ±. 13.0 vs. 17.8. ±. 5.6. μg/ml; P<. 0.05) and lower plasma nitrite levels (104.5. ±. 84.3 vs. 177.2. ±. 151.3 nM; P<. 0.05) in PE compared to HP. We found a significant positive correlation between these markers in HP (r=. 0.3; P<. 0.05), but no correlation in PE. However, when we grouped PE women regarding ADMA levels (low and high levels), a strong positive correlation was found in the group with lower ADMA levels (r=. 0.67; P<. 0.05), suggesting that high ADMA concentrations may interfere with the physiological activation of eNOS by adiponectin in PE. Conclusions: Our findings showed higher levels of adiponectin and lower nitrite levels in PE compared to HP, and these levels were positively correlated in HP and in PE presenting lower concentrations of ADMA. © 2013 Elsevier B.V.


Luizon M.R.,University of Sao Paulo | Sandrim V.C.,Nucleo de Pos Graduacao e Pesquisa | Palei A.C.T.,University of Campinas | Lacchini R.,University of Sao Paulo | And 3 more authors.
Hypertension Research | Year: 2012

Polymorphisms of the endothelial nitric oxide synthase (eNOS), matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) genes were shown to be associated with hypertensive disorders of pregnancy. However, epistasis is suggested to be an important component of the genetic susceptibility to preeclampsia (PE). The aim of this study was to characterize the interactions among these genes in PE and gestational hypertension (GH). Seven clinically relevant polymorphisms of eNOS (T-786C, rs2070744, a variable number of tandem repeats in intron 4 and Glu298Asp, rs1799983), MMP-9 (C-1562T, rs3918242 and-90(CA) 13-25, rs2234681) and VEGF (C-2578A, rs699947 and G-634C, rs2010963) were genotyped by TaqMan allelic discrimination assays or PCR and fragment separation by electrophoresis in 122 patients with PE, 107 patients with GH and a control group of 102 normotensive pregnant (NP) women. A robust multifactor dimensionality reduction analysis was used to characterize gene-gene interactions. Although no significant genotype combinations were observed for the comparison between the GH and NP groups (P0.05), the combination of MMP-9-1562CC with VEGF-634GG was more frequent in NP women than in women with PE (P0.05). Moreover, the combination of MMP-9-1562CC with VEGF-634CC or MMP-9-1562CT with VEGF-634CC or-634GG was more frequent in women with PE than in NP women (P0.05). These results are obscured when single polymorphisms in these genes are considered and suggest that specific genotype combinations of MMP-9 and VEGF contribute to PE susceptibility. © 2012 The Japanese Society of Hypertension All rights reserved.


Sandrim V.C.,São Paulo State University | Palei A.C.T.,University of Campinas | Eleuterio N.,Nucleo de Pos Graduacao e Pesquisa | Tanus-Santos J.E.,University of Sao Paulo | Cavalli R.C.,University of Sao Paulo
Archives of Gynecology and Obstetrics | Year: 2015

Introduction: Vascular endothelial growth factor (VEGF) is relevant for healthy pregnancy, and abnormalities in VEGF functions have been associated with hypertensive disorders of pregnancy. Our group recently demonstrated that VEGF genetic polymorphisms affect the susceptibility to preeclampsia (PE). Objective: Therefore, in this study our aim is to examine whether VEGF polymorphisms affect the antihypertensive responses in women with PE. Methods: We studied 113 white PE women who were stratified according to blood pressure levels after antihypertensive treatment (46 responsive, R group and 67 non-responsive, NR group). We then compared the frequencies of two VEGF genetic polymorphisms (C-2578A and G-634C) between R and NR groups. Results: We found no significant differences in genotype or allele distributions between R and NR groups (P > 0.05). In addition, no difference was observed in overall distribution of haplotypes (P > 0.05). Conclusion: Our data suggest that VEGF polymorphisms do not affect responsiveness to the antihypertensive therapy in PE. © 2014, Springer-Verlag Berlin Heidelberg.


Sandrim V.C.,Nucleo de Pos Graduacao e Pesquisa | Luizon M.R.,University of Sao Paulo | Izidoro-Toledo T.C.,University of Sao Paulo | Coelho E.B.,University of Sao Paulo | And 2 more authors.
Journal of Human Hypertension | Year: 2013

We examined whether vascular endothelial growth factor (VEGF) polymorphisms (C-2578A, G-1154A and G-634C) are associated with hypertension, response to antihypertensive therapy and nitric oxide (NO) formation. Substudy 1 compared the distribution of VEGF genotypes and haplotypes in 178 patients with arterial hypertension (100 whites and 78 blacks) and 186 healthy controls (115 whites and 71 blacks). Substudy 2 compared the distribution of VEGF markers in 82 patients with controlled hypertension, 89 patients with resistant hypertension and 101 normotensive (NT) patients. In substudy 3, plasma nitrite/nitrate (NOx) levels were determined (chemiluminescence assay) in 64 NT subjects and 48 hypertensive (HTN) subjects, and the distribution of VEGF markers was compared in subjects having low NOx with subjects having high NOx. Although the substudy 1 showed no differences in genotypes or allele distributions for the three VEGF polymorphisms between NT and HTN subjects, the C-A-G haplotype was more common in white NT subjects than in the white HTN subjects, and the C-A-C haplotype was more frequent in black and white HTN subjects than in black and white NT subjects. The substudy 2 showed similar results, with no differences between responsive and resistant HTN subjects. The substudy 3 showed that the C-A-G haplotype, which had a protective effect against hypertension, was significantly more common in subjects with higher NOx concentrations than in subjects with lower NOx concentrations. VEGF haplotypes are associated with hypertension, and the haplotype associated with normotension was more common in subjects with increased NO formation, possibly offering a mechanistic clue for our findings. © 2013 Macmillan Publishers Limited.


Pontillo A.,University of Sao Paulo | Reis E.C.,University of Sao Paulo | Bricher P.N.,University of Sao Paulo | Vianna P.,Federal University of Rio Grande do Sul | And 4 more authors.
American Journal of Reproductive Immunology | Year: 2015

Problem: Augmented levels of IL-1ß have been pointed out as an important pathogenic factor for preeclampsia development. Inflammasome is the cytoplasmic complex responsible for pro-IL1ß cleavage and IL-1ß secretion. Aim of the study was to evaluate the association between polymorphisms in inflammasome' genes and preeclampsia. Method of study: Selected polymorphisms in inflammasome genes (NLRP1, NLRP3, CARD8, and IL1B) were analyzed in 286 Brazilian women with and 309 without preeclampsia. Results and Conlclusions: The NLRP1 variant rs12150220 (L155H) was associated with the development of preeclampsia (OR = 1.58), suggesting a role of this inflammasome receptor in the pathogenesis of this multifactorial disorder. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Fernandes K.S.D.S.,University of Sao Paulo | Brum D.G.,University of Sao Paulo | Palei A.C.,University of Sao Paulo | Sandrim V.C.,Nucleo de Pos Graduacao e Pesquisa | And 3 more authors.
Journal of Neuroimmunology | Year: 2012

We have described that MMP-9 C -1562T and (CA) n polymorphisms contribute to multiple sclerosis (MS). Here, we evaluate whether plasma MMP-9 levels are related to disease severity, drug therapy resistance and polymorphisms. For sub-study 1, 36 patients with MS and 35 controls were recruited. For sub-study 2, 88 individuals (53 patients and 35 controls) were included in a cross-sectional analysis. MS patients presented higher MMP-9 activity (1.4±0.18 versus 0.93±0.18A.U. for control, P<0.05). Drug-therapy resistant individuals exhibited increased MMP-9 activity (1.96±0.25 versus 1.21±0.09A.U. for non-resistant patients). EDSS score was also related to MMP-9 levels. The CT+TT and HH genotypes had higher MMP-9 levels as compared to patients carrying the CC and LL. Drug therapy resistance, disease severity, MMP-9 plasma activity and polymorphisms are associated with MS. © 2012 Elsevier B.V.


PubMed | São Paulo State University, Nucleo de Pos graduacao e Pesquisa and University of Sao Paulo
Type: Journal Article | Journal: Molecular biology reports | Year: 2016

Plasma matrix metalloproteinase (MMP)-9 is a predictor of cardiovascular mortality, and MMP-9 polymorphisms affect plasma MMP-9 levels. However, no study examined whether MMP-9 haplotypes affect MMP-9 levels in obese adults. We examined whether MMP-9 polymorphisms and haplotypes are associated with obesity, and whether they affect MMP-9 levels in obese subjects. We examined the plasma levels of MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in 105 subjects with normal weight (controls), 100 obese subjects, and 156 obese subjects with 3 metabolic risk factors (MRFs). We determined genotypes for three polymorphisms: C-1562T (rs3918242), Q279R (A>G, rs17576), and R668Q (G>A, rs17577). MMP-9 levels and activity (MMP-9/TIMP-1 ratio) were higher in obese subjects than in controls (P<0.05). However, MMP-9 levels were higher in obese subjects with 3 MRFs than in obese subjects (P<0.05). Obese subjects with 3 MRFs carrying the GA+AA genotypes for R668Q (G>A) polymorphism had higher MMP-9 levels than subjects carrying the AA genotype (P<0.05). The T, G, A haplotype was more common in both groups of obese subjects than in controls (OR 3.95 and 4.39, respectively; P<0.01). Notably, obese subjects with 3 MRFs carrying the T, G, A haplotype had higher MMP-9 levels than subjects carrying the C, A, G reference haplotype (P<0.05). The T, G, A haplotype was associated with an increased risk of obesity and affected MMP-9 levels in obese subjects with 3 MRFs. Our findings suggest that plasma MMP-9 levels and MMP-9 haplotypes may help to discriminate obese subjects at an increased cardiovascular risk.


Fernandes K.S.,Nucleo de Pos Graduacao e Pesquisa | Sandrim V.C.,Nucleo de Pos Graduacao e Pesquisa
Molecular and Cellular Biochemistry | Year: 2012

The increase in plasminogen activator inhibitor type 1 (PAI-1) has been described as a risk factor to thrombosis-related diseases. In addition, it has been demonstrated that the variant 4G of polymorphism 4G/5G located in promoter region of PAI-1 gene is associated with higher PAI-1 levels. We investigate the role of this polymorphism on circulating PAI-1 concentration in a population of 57 obese women (23%, 4G/4G; 49%, 4G/5G and 28%, 5G/5G genotypes). Our results demonstrate a genotype-specific modulation on PAI-1 levels in obese women, thus 5G/5G genotype presented significantly lower levels of plasma PAI-1 when compared to 4G/4G group (46 ± 19 ng/mL vs. 63 ± 13 ng/mL, respectively). Our findings indicate that obese carriers of 4G/4G genotype may have increased risk to develop thrombotic diseases. © Springer Science+Business Media, LLC. 2012.

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