ANA PAULA PACANARO

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Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina

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  • article 11 Citação(ões) na Scopus
    MMP9 integrates multiple immunoregulatory pathways that discriminate high suppressive activity of human mesenchymal stem cells
    (2017) LAVINI-RAMOS, Carolina; SILVA, Hernandez Moura; SOARES-SCHANOSKI, Alessandra; MONTEIRO, Sandra Maria; FERREIRA, Ludmila Rodrigues Pinto; PACANARO, Ana Paula; GOMES, Samirah; BATISTA, Janaina; FAE, Kellen; KALIL, Jorge; COELHO, Veronica
    The mechanisms underlying mesenchymal stem cells' (MSC) suppressive potency are largely unknown. We here show that highly suppressive human adipose tissue-derived MSC (AdMSC) display and induce a differential immunologic profile, upon ongoing AdMSC suppressive activity, promoting: (i) early correlated inhibition of IFN-gamma and TNF-alpha production, along IL-10 increase, (ii) CD73(+) Foxp3(+) Treg subset expansion, and (iii) specific correlations between gene expression increases, such as: MMP9 correlated with CCL22, TNF, FASL, RUNX3, and SEMAD4 in AdMSC and, in T cells, MMP9 upregulation correlated with CCR4, IL4 and TBX21, among others, whereas MMP2 correlated with BCL2 and LRRC31. MMP9 emerged as an integrating molecule for both AdMSC and T cells in molecular networks built with our gene expression data, and we confirmed upregulation of MMP9 and MMP2 at the protein level, in AdMSC and T cells, respectively. MMP2/9 inhibition significantly decreased AdMSC suppressive effect, confirming their important role in suppressive acitivity. We conclude that MMP9 and 2 are robust new players involved in human MSC immunoregulatory mechanisms, and the higher suppressive activity correlates to their capacity to trigger a coordinated action of multiple specific molecules, mobilizing various immunoregulatory mechanisms.
  • article 24 Citação(ões) na Scopus
    Gene Expression of Sirtuin-1 and Endogenous Secretory Receptor for Advanced Glycation End Products in Healthy and Slightly Overweight Subjects after Caloric Restriction and Resveratrol Administration
    (2018) ROGGERIO, Alessandra; STRUNZ, Celia M. Cassaro; PACANARO, Ana Paula; LEAL, Dalila Pinheiro; TAKADA, Julio Y.; AVAKIAN, Solange D.; MANSUR, Antonio de Padua
    Sirtuin-1 (Sirt-1) and an endogenous secretory receptor for an advanced glycation end product (esRAGE) are associated with vascular protection. The purpose of this study was to examine the effects of resveratrol (RSV) and caloric restriction (CR) on gene expression of Sirt-1 and esRAGE on serum levels of Sirt1 and esRAGE in healthy and slightly overweight subjects. The study included 48 healthy subjects randomized to 30 days of RSV (500 mg/day) or CR (1000 cal/day). Waist circumference (p = 0.011), TC (p = 0.007), HDL (p = 0.031), non-HDL (p = 0.025), ApoA1 (p = 0.011), and ApoB (p = 0.037) decreased in the CR group. However, TC (p = 0.030), non-HDL (p = 0.010), ApoB (p = 0.034), and HOMA-IR (p = 0.038) increased in the RSV group. RSV and CR increased serum levels of Sirt-1, respectively, from 1.06 +/- 0.71 ng/mL to 5.75 +/- 2.98 ng/mL (p < 0.0001) and from 1.65 +/- 1.81 ng/mL to 5.80 +/- 2.23 ng/mL (p < 0.0001). esRAGE serum levels were similar in RSV (p = NS) and CR (p = NS) groups. Significant positive correlation was observed between gene expression changes of Sirt-1 and esRAGE in RSV (r = 0.86; p < 0.0001) and in CR (r = 0.71; p < 0.0001) groups, but not for the changes in serum concentrations. CR promoted increases in the gene expression of esRAGE (post/pre). Future long-term studies are needed to evaluate the impact of these outcomes on vascular health.
  • article 13 Citação(ões) na Scopus
    Biomarkers for prediction of mortality in left-sided infective endocarditis
    (2020) SICILIANO, Rinaldo F.; GUALANDRO, Danielle M.; BITTENCOURT, Marcio Sommer; PAIXAO, Milena; MARCONDES-BRAGA, Fabiana; SOEIRO, Alexandre de Matos; STRUNZ, Celia; PACANARO, Ana Paula; PUELACHER, Christian; TARASOUTCHI, Flavio; SOMMA, Salvatore Di; CARAMELLI, Bruno; OLIVEIRA JUNIOR, Mucio Tavares de; MANSUR, Alfredo Jose; MUELLER, Christian; BARRETTO, Antonio Carlos Pereira; STRABELLI, Tania Mara Varejao
    Background: Evidence regarding biomarkers for risk prediction in patients with infective endocarditis (IE) is limited. We aimed to investigate the value of a panel of biomarkers for the prediction of in-hospital mortality in patients with IE. Methods: Between 2016 and 2018, consecutive IE patients admitted to the emergency department were prospectively included. Blood concentrations of nine biomarkers were measured at admission (D0) and on the seventh day (D7) of antibiotic therapy: C-reactive protein (CRP), sensitive troponin I (s-cTnI), procalcitonin, B-type natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL), interleukin 6 (IL6), tumor necrosis fator a (TNF-a), proadrenomedullin, alpha-1-acid glycoprotein, and galectin 3. The primary endpoint was in-hospital mortality. Results: Among 97 patients, 56% underwent cardiac surgery, and in-hospital mortality was 27%. At admission, six biomarkers were independent predictors of in-hospital mortality: s-cTnI (OR 3.4; 95%CI 1.8-6.4; P < 0.001), BNP (OR 2.7; 95%CI 1.4-5.1; P = 0.002), IL-6 (OR 2.06; 95%CI 1.3-3.7; P = 0.019), procalcitonin (OR 1.9; 95%CI 1.1-3.2; P = 0.018), TNF-alpha (OR 1.8; 95%CI 1.1-2.9; P = 0.019), and CRP (OR 1.8; 95%CI 1.0-3.3; P = 0.037). At admission, S-cTnI provided the highest accuracy for predicting mortality (area under the ROC curve: s-cTnI 0.812, BNP 0.727, IL-6 0.734, procalcitonin 0.684, TNF-alpha 0.675, CRP 0.670). After 7 days of antibiotic therapy, BNP and inflammatory biomarkers improved their performance (s-cTnI 0.814, BNP 0.823, IL-6 0.695, procalcitonin 0.802, TNF-alpha 0.554, CRP 0.759). Conclusion: S-cTnI concentration measured at admission had the highest accuracy for mortality prediction in patients with IE. (C) 2020 The Authors.
  • article 9 Citação(ões) na Scopus
    Influence of the treatment of periodontal disease in serum concentration of sirtuin 1 and mannose-binding lectin
    (2020) CARIBE, Perola Michelle Vasconcelos; VILLAR, Cristina Cunha; ROMITO, Giuseppe Alexandre; PACANARO, Ana Paula; STRUNZ, Celia Maria Cassaro; TAKADA, Julio Yoshio; CESAR, Luiz Antonio Machado; MANSUR, Antonio de Padua
    Background Increased levels of periodontal pathogens disrupt the homeostasis between the host and its microbiota and increase susceptibility to periodontal diseases. Periodontitis increases the serum concentration of mannose-binding lectin (MBL), which exacerbates local inflammatory processes. In animal studies, sirtuin 1 (SIRT1) was associated with protection against inflammation. This study analyzed the influence of non-surgical periodontal treatment on serum levels of MBL and SIRT1. Methods Forty patients with periodontitis and 38 periodontally healthy individuals (aged 45 to 79 years) were included. Periodontitis patients received scaling and root planing using machine driven and hand instruments. Clinical parameters, inflammatory biomarkers, MBL, and SIRT1 levels were measured at baseline and at post-treatment. Results For all patients, an inverse correlation was observed between serum concentrations of MBL and SIRT1 (r = -0.30; P = 0.006). Periodontal treatment reduced serum concentrations of MBL (1,099.35 +/- 916.59 to 861.42 +/- 724.82 ng/mL; P < 0.001) and C-reactive protein (6.05 +/- 8.99 to 2.49 +/- 2.89 mg/L; P = 0.009). By contrast, SIRT1 serum levels increased (1.06 +/- 1.03 to 1.66 +/- 1.64 ng/mL; P < 0.001) following periodontal treatment. Conclusions Periodontal treatment was associated with decreased serum concentrations of MBL and CRP and increased serum levels of SIRT1. Prospective studies are needed to assess the impact of these biomarkers on pathophysiology of periodontitis.
  • article 7 Citação(ões) na Scopus
    Prospective, case-controlled study evaluating serum concentration of sirtuin-1 and mannose-binding lectin in patients with and without periodontal and coronary artery disease
    (2020) CARIBE, Perola Michelle Vasconcelos; VILTAR, Cristina Cunha; ROMITO, Guiseppe Alexandre; TAKADA, Julio Yoshio; PACANARO, Ana Paula; STRUNZ, Celia Maria Cassaro; CESAR, Luiz Antonio Machado; MANSUR, Antonio de Padua
    Background: Atherosclerosis and periodontal disease (PD) are inflammatory diseases that have been shown in studies to have a direct association. Mannose-binding lectin (MBL) is an immune system protein that binds to periodontal pathogens favoring phagocytosis. Conversely, increased serum sirtuin-1 (SIRT1) concentration reduces the inflammatory process. Methods: This was a prospective, case-controlled study that analyzed serum concentration of biomarkers in patients with or without coronary artery disease (CAD) and PD. A total of 78 patients were evaluated: 20 healthy individuals, 18 patients with CAD, 20 patients with PD, and 20 patients with both PD and CAD. Clinical and laboratory characteristics were analyzed before and after nonsurgical treatment of PD and also at two equivalent times in patients without PD. Serum MBL and SIRT1 concentration were analyzed by enzyme-linked immunosorbent assay. Results: A negative correlation was observed between changes in serum concentration of MBL and SIRT1 (r = -0.30; p = 0.006). Comparison between pre- and post-treatment of PD showed a reduction in MBL levels (886.27 +/- 906.72 versus 689.94 +/- 808.36; p = 0.002) and an increase in SIRT1 values (0.80 +/- 1.01 versus 1.49 +/- 1.55; p = 0.005) in patients with PD and without CAD. The same result was observed in patients with PD and CAD for MBL and SIRT1, respectively, of 1312.43 +/- 898.21 versus 1032.90 +/- 602.52 (p = 0.010) and 1.32 +/- 1.0 versus 1.82 +/- 1.75 (p = 0.044). Conclusion: PD treatment reduced MBL serum concentration and increased SIRT1 serum concentration in patients with and without CAD.
  • conferenceObject
    Biomarkers for the prediction of mortality in patients with infective endocarditis
    (2018) SICILIANO, R. F.; GUALANDRO, D. M.; FELICIO, M. S.; PAIXAO, M. R.; MARCONDES-BRAGA, F. G.; OLIVEIRA JR., M. T.; SOEIRO, A.; TARASOUTCH, F.; CARAMELLI, B.; STRUNZ, C.; PACANARO, A. P.; BITTENCOURT, M. S.; MANSUR, A. J.; PEREIRA-BARRETTO, A. C.; STRABELLI, T. M. V.
  • article 18 Citação(ões) na Scopus
    Down-regulation of fibroblast growth factor 2 and its co-receptors heparan sulfate proteoglycans by resveratrol underlies the improvement of cardiac dysfunction in experimental diabetes
    (2017) STRUNZ, Celia Maria Cassaro; ROGGERIO, Alessandra; CRUZ, Paula Lazara; PACANARO, Ana Paula; SALEMI, Vera Maria Cury; BENVENUTI, Luiz Alberto; MANSUR, Antonio de Padua; IRIGOYEN, Maria Claudia
    Cardiac remodeling in diabetes involves cardiac hypertrophy and fibrosis, and fibroblast growth factor 2 (FGF2) is an important mediator of this process. Resveratrol, a polyphenolic antioxidant, reportedly promotes the improvement of cardiac dysfunction in diabetic rats. However, little information exists linking the amelioration of the cardiac function promoted by resveratrol and the expression of FGF2 and its co-receptors, heparan sulfate proteoglycans (HSPGs: Glypican-1 and Syndecan-4), in cardiac muscle of Type 2 diabetic rats. Diabetes was induced experimentally by the injection of streptozotocin and nicotinamide, and the rats were treated with resveratrol for 6 weeks. According to our results, there is an up-regulation of the expression of genes and/or proteins of Glypican1, Syndecan-4, FGF2, peroxisome proliferator-activated receptor gamma and AMP-activated protein kinase in diabetic rats. On the other hand, resveratrol treatment promoted the attenuation of left ventricular diastolic dysfunction and the down-regulation of the expression of all proteins under study. The trigger for the changes in gene expression and protein synthesis promoted by resveratrol was the presence of diabetes. The negative modulation conducted by resveratrol on FGF2 and HSPGs expression, which are involved in cardiac remodeling, underlies the amelioration of cardiac function. (C) 2016 The Authors.
  • article 4 Citação(ões) na Scopus
    The Interplay of Sirtuin-1, LDL-Cholesterol, and HDL Function: A Randomized Controlled Trial Comparing the Effects of Energy Restriction and Atorvastatin on Women with Premature Coronary Artery Disease
    (2022) LEAL, Dalila Pinheiro; GONCALINHO, Gustavo Henrique Ferreira; TAVONI, Thauany Martins; KUWABARA, Karen Lika; PACCANARO, Ana Paula; FREITAS, Fatima Rodrigues; STRUNZ, Celia Maria Cassaro; CESAR, Luiz Antonio Machado; MARANHAO, Raul Cavalcante; MANSUR, Antonio de Padua
    Introduction: HDL function has gained prominence in the literature as there is a greater predictive capacity for risk in early coronary artery disease when compared to the traditional parameters. However, it is unclear how dietary energy restriction and atorvastatin influence HDL function. Methods: A randomized controlled trial with 39 women with early CAD divided into three groups (n = 13): energy restriction (30% of VET), atorvastatin (80 mg), and control. Analyses of traditional biochemical markers (lipid and glucose profile), circulating Sirt-1, and HDL function (lipid composition, lipid transfer, and antioxidant capacity). Results: Participants' mean age was 50.5 +/- 3.8 years. Energy restriction increased Sirt-1 by 63.6 pg/mL (95%CI: 1.5-125.7; p = 0.045) and reduced BMI by 0.8 kg/m(2) (95%CI: -1.349--0.273; p = 0.004) in a manner independent of other cardiometabolic factors. Atorvastatin reduced LDL-c by 40.0 mg/dL (95%CI: -69.910--10.1; p = 0.010). Increased Sirt-1 and reduced BMI were independently associated with reduced phospholipid composition of HDL (respectively, beta = -0.071; CI95%:-0.136--0.006; p = 0.033; beta = 7.486; CI95%:0.350-14.622; p = 0.040). Reduction in BMI was associated with lower HDL-free cholesterol (beta = 0.818; CI95%:0.044-1.593; p = 0.039). LDL-c reduction by statins was associated with reduced maximal lipid peroxide production rate of HDL (beta = 0.002; CI95%:0.000-0.003; p = 0.022) and total conjugated diene generation (beta = 0.001; CI95%:0.000-0.001; p = 0.029). Conclusion: This study showed that energy restriction and atorvastatin administration were associated with changes in lipid profile, serum Sirt-1 concentrations, and HDL function.