Navegando por Palavras-chave "PAI-1"
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- ItemSomente MetadadadosFibrinolytic dysfunction after gestation is associated to components of insulin resistance and early type 2 diabetes in latino women with previous gestational diabetes(Elsevier B.V., 2007-12-01) Morimitsu, Lilian K.; Fusaro, Annunciata S.; Sanchez, Victor H.; Hagemann, Cristiane C. F.; Bertini, Anna Maria; Dib, Sergio A.; Universidade Federal de São Paulo (UNIFESP)Among patients with metabolic syndrome (MS), atherosclerosis and abnormal fibrinolytic function are frequently present, mostly owing to an increase in plasminogen activator inhibitor-1(PAI-1). We analyze PAI-1 in pregnant women, both normal and with gestational diabetes (GDM) and postpartum regarding its correlation to MS surrogates. Clinical characteristics, glucose tolerance (100 g-OGTT), lipids, PAI-1 antigen, insulin sensitivity (HOMA-S), and pancreatic P-cell function (HOMA-B) were investigated in 34 women. Eleven had normal glucose tolerance (NGT) during pregnancy and 23 had GDM (all GAD antibodies-negative). All patients were studied at 28-34 weeks of gestation and 16-24 weeks after delivery (75 g-OGTT). Parameters of interest were determined using commercial test systems. During pregnancy, PAI-1 was not statistically different between NGT and GDM (47 +/- 25 ng/ml versus 47 +/- 28 ng/ml, p = 0.9). After gestation, 19 (56%) women had NGT (11 of them from previous NGT A group) and 15 (44%) had impaired glucose tolerance (IGT) or DM. the IGT (IGT + DM) group had higher PAI-1 (p = 0.01), which did not decreased after delivery NGT-NGT before and after delivery (47 +/- 25 ng/ml versus 6 +/- 5 ng/ml; p < 0.001), GDM-NGT (62 +/- 36 ng/ml versus 14 +/- 15 ng/ml; p = 0.001) and GDM-IGT (39 +/- 20 ng/ml versus 27 +/- 23 ng/ml; p = 0. 15). PAI-1 levels were positively correlated (p < 0.05) to total cholesterol (r, = 0.37), triglycerides (r,, = 0.48), fasting plasma glucose (r(s), = 0.52), 2-h plasma glucose in the OGTT (r(s) = 0.58) and were negatively correlated (p < 0.05) with HOMA-S (rs = -0.42) and HOMA-B (r, = -0.38). Fibrinolytic dysfunction is still present in GDM women and is associated with early development of IGT or T2DM. PAI correlated with surrogate markers of MS levels and may identify a group of women at risk for macroangiopathy. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
- ItemSomente MetadadadosImprovement in HOMA-IR is an independent predictor of reduced carotid intima-media thickness in obese adolescents participating in an interdisciplinary weight-loss program(Nature Publishing Group, 2011-02-01) Sanches, Priscila de Lima [UNIFESP]; Mello, Marco Tulio de [UNIFESP]; Elias, Natalia; Fonseca, Francisco Antonio Helfenstein [UNIFESP]; Piano, Aline de [UNIFESP]; Carnier, June [UNIFESP]; Oyama, Lila Missae [UNIFESP]; Tock, Lian [UNIFESP]; Tufik, Sergio [UNIFESP]; Dâmaso, Ana Raimunda [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The aim of this study was to verify whether a 1-year interdisciplinary weight-loss program improved common carotid artery intima-media thickness (IMT) and whether insulin resistance and/or inflammation (as measured by the markers plasminogen activator inhibitor type-1 and adiponectin) might underlie obesity in adolescents. A group of 29 post-pubescent obese adolescents were submitted to an interdisciplinary intervention over the course of 1 year. Common carotid artery IMT was determined ultrasonographically. Body composition, blood pressure (BP), glycemia, insulinemia, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile and adipokine concentrations were analyzed before and after the intervention. the interdisciplinary weight-loss program promoted a significant improvement in body composition, insulin concentration, HOMA-IR, lipid profile, BP and inflammatory state, in addition to significantly decreasing the common carotid artery IMT. Furthermore, this study demonstrated that the difference between baseline and final values of HOMA-IR (Delta HOMA-IR) was negatively correlated with concomitant changes in the adiponectin concentration (Delta adiponectin; r=-0.42; P=0.02) and positively correlated with changes in common carotid artery IMT (Delta carotid IMT; r=0.41; P=0.03). Multiple regression analysis adjusted by age, cardiovascular risk factors and inflammatory markers showed that Delta HOMA-IR was an independent predictor of significant changes in common carotid artery IMT. This investigation demonstrated that an interdisciplinary weight-loss program promoted a reduction of the common carotid artery IMT in obese Brazilian adolescents, and the improvement of HOMA-IR was an independent predictor of carotid IMT changes in this population. Hypertension Research (2011) 34, 232-238; doi: 10.1038/hr.2010.225; published online 2 December 2010
- ItemSomente MetadadadosThe Role of PAI-1 and Adiponectin on the Inflammatory State and Energy Balance in Obese Adolescents with Metabolic Syndrome(Springer, 2012-06-01) Corgosinho, Flavia Campos [UNIFESP]; Piano, Aline de [UNIFESP]; Sanches, Priscila de Lima [UNIFESP]; Campos, Raquel Munhoz da Silveira [UNIFESP]; Silva, Patricia Leao da [UNIFESP]; Carnier, June [UNIFESP]; Oyama, Lila Missae [UNIFESP]; Tock, Lian [UNIFESP]; Tufik, Sergio [UNIFESP]; Mello, Marco Tulio de [UNIFESP]; Dâmaso, Ana Raimunda [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Obesity is a chronic inflammatory disease and is considered a risk factor for metabolic syndrome. in this study, 57 obese adolescents with and without metabolic syndrome underwent 1 year of weight loss therapy. At baseline, the metabolic syndrome (MS) patients presented higher values of PAI-1 than the non-metabolic syndrome patients (n-MS). After therapy, significant improvements in anthropometrics and biochemical, inflammatory, and neuroendocrine variables were observed in both groups. However, the n-MS group presented better results than the MS group. Indeed, we found positive correlations in both groups between PAI-1 and neuropeptide Y (NPY) and between PAI-1 and NPY/AgRP. Inflammatory biomarkers may thus play a role in energy balance. the clinical trial registration number is NCT01358773.
- ItemSomente MetadadadosSaturated Fatty Acid Intake Can Influence Increase in Plasminogen Activator Inhibitor-1 in Obese Adolescents(Georg Thieme Verlag Kg, 2014-04-01) Masquio, Deborah Cristina Landi [UNIFESP]; Piano, Aline de [UNIFESP]; Campos, Raquel Munhoz da Silveira [UNIFESP]; Sanches, Priscila de Lima [UNIFESP]; Corgosinho, Flavia Campos [UNIFESP]; Carnier, June [UNIFESP]; Oyama, Lila Missae [UNIFESP]; Nascimento, Claudia Maria da Penha Oller do [UNIFESP]; Mello, Marco Tulio de [UNIFESP]; Tufik, Sergio [UNIFESP]; Dâmaso, Ana Raimunda [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The aim of this study was to verify if saturated fatty acid intake adjusted by tertiles can influence metabolic, inflammation, and plasminogen activator inhibitor-1 (PAI-1) in obese adolescents. Body mass, height, body mass index, waist circumference, blood pressure, and body composition of 108 obese adolescents were obtained. Fasting glucose, insulin, PAI-1, and CRP were determined. Insulin resistance was assessed by Homeostasis Model Assessment (HOMA-IR) and insulin sensitivity by Quantitative Insulin Sensitivity Check Index (QUICKI). Dietetic intake was estimated by a 3-day dietary record, and volunteers were divided according to consumption of saturated fatty acids: tertile 1 [Low Saturated Fatty Acid Intake (Low-SFA): <= 12.14 g], tertile 2 [Moderate Saturated Fatty Intake (Moderate SFA intake): 12.15-20.48 g], and tertile 3 [High Saturated Fatty Acid Intake (High-SFA Intake); >20.48 g]. Statistical analysis was performed using STATISTICA 7.0 software and the significance level was set at p < 0.05. the most important finding in the present study is that Moderate and High-SFA intakes presented significantly higher values of PAI-1 than Low-SFA Intake. PAI-1 was positively associated with saturated fatty intake, waist circumference, mean blood pressure, and HOMA-IR. SFA intake was predictor of PAI-1 independent of body fat, HOMA-IR and total-cholesterol. in addition, PAI-1 was an independent predictor of blood pressure. HOMA-IR and QUICKI presented significantly higher and lower, respectively, in High-SFA compared to Moderate-SFA intake. High-SFA influenced cardiovascular disease risks, since it increased PAI-1 and insulin resistance, and decreased insulin sensibility, leading to vicious cycle among food ingestion, pro-thrombotic state, and cardiovascular risks in obese adolescents. Supporting Information for this article is available online at http://www.thieme-connect.de/ejournals/toc/hmr
- ItemSomente MetadadadosVitronectin dictates intraglomerular fibrinolysis in immune-mediated glomerulonephritis(Federation Amer Soc Exp Biol, 2011-10-01) Mesnard, Laurent; Rafat, Cedric; Vandermeersch, Sophie; Hertig, Alexandre; Cathelin, Dominique; Xu-Dubois, Yi-Chun; Jouanneau, Chantal; Keller, Alexandre Castro [UNIFESP]; Ribeil, Jean-Antoine; Leite-de-Moraes, Maria C.; Rondeau, Eric; Univ Paris 06; Hop Necker Enfants Malad; Universidade Federal de São Paulo (UNIFESP)During human glomerulonephritis, the severity of injuries correlates with glomerular fibrin deposits, which are tightly regulated by the intraglomerular fibrinolytic system. Here, we evaluated the role of vitronectin (VTN; also known as complement S protein), the principal cofactor of the plasminogen activator inhibitor-1 (PAI-1), in a mouse model of acute glomerulonephritis. We found that in mice subjected to nephrotoxic serum, the absence of VTN resulted in a lower glomerular PAI-1 activity and a higher glomerular fibrinolytic activity. Challenged VTN-/- mice displayed significantly less fibrin deposits, proteinuria, and renal failure than their wild-type counterparts. Notably, this protective effect afforded by VTN deficiency was still observed after a C3 depletion. Finally, the injection of VTN+/+ serum in VTN-/- mice induced the glomerular deposition of VTN, increased PAI-1 deposition, decreased glomerular fibrinolytic activity, and aggravated glomerular injury. As in mice, abundant glomerular VTN deposits were also observed in patients with severe glomerulonephritis. Here, we show that plasma-exchange therapy, admittedly beneficial in this clinical context, induces a significant depletion in circulating VTN, which might modulate PAI-1 activity locally and accelerate the clearance of fibrin deposits in the glomeruli. Collectively, these results demonstrate that VTN exerts a deleterious role independently from complement, by directing PAI-dependent fibrinolysis in the glomerular compartment.-Mesnard, L., Rafat, C., Vandermeersch, S., Hertig, A., Cathelina, D., Xu-Dubois, Y. -C., Jouanneau, C., Castro Keller, A., Ribeil, J. -A., Leite-de-Moraes, M. C., Rondeau, E. Vitronectin dictates intraglomerular fibrinolysis in immune-mediated glomerulonephritis. FASEB J. 25, 3543-3553 (2011). www.fasebj.org