NOEDIR ANTONIO GROPPO STOLF
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Cardio-Pneumologia, Faculdade de Medicina - Docente
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
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- Polymorphism in the Alpha Cardiac Muscle Actin 1 Gene Is Associated to Susceptibility to Chronic Inflammatory Cardiomyopathy(2013) FRADE, Amanda Farage; TEIXEIRA, Priscila Camilo; IANNI, Barbara Maria; PISSETTI, Cristina Wide; SABA, Bruno; WANG, Lin Hui Tzu; KURAMOTO, Andreia; NOGUEIRA, Luciana Gabriel; BUCK, Paula; DIAS, Fabricio; GINIAUX, Helene; LLORED, Agnes; ALVES, Sthefanny; SCHMIDT, Andre; DONADI, Eduardo; MARIN-NETO, Jose Antonio; HIRATA, Mario; SAMPAIO, Marcelo; FRAGATA, Abilio; BOCCHI, Edimar Alcides; STOLF, Antonio Noedir; FIORELLI, Alfredo Inacio; SANTOS, Ronaldo Honorato Barros; RODRIGUES, Virmondes; PEREIRA, Alexandre Costa; KALIL, Jorge; CUNHA-NETO, Edecio; CHEVILLARD, ChristopheAims: Chagas disease, caused by the protozoan Trypanosoma cruzi is endemic in Latin America, and may lead to a life-threatening inflammatory dilated, chronic Chagas cardiomyopathy (CCC). One third of T. cruzi-infected individuals progress to CCC while the others remain asymptomatic (ASY). A possible genetic component to disease progression was suggested by familial aggregation of cases and the association of markers of innate and adaptive immunity genes with CCC development. Since mutations in multiple sarcomeric genes, including alpha-cardiac actin (ACTC1) have been involved in hereditary dilated cardiomyopathy, we investigated the involvement of the ACTC1 gene in CCC pathogenesis. Methods and Results: We conducted a proteomic and genetic study on a Brazilian study population. The genetic study was done on a main cohort including 118 seropositive asymptomatic subjects and 315 cases and the replication was done on 36 asymptomatic and 102 CCC cases. ACTC1 protein and mRNA levels were lower in myocardial tissue from patients with end-stage CCC than those found in hearts from organ donors. Genotyping a case-control cohort of CCC and ASY subjects for all informative single nucleotide polymorphism (SNP) in the ACTC1 gene identified rs640249 SNP, located at the 5' region, as associated to CCC. Associations are borderline after correction for multiple testing. Correlation and haplotype analysis led to the identification of a susceptibility haplotype. Functional assays have shown that the rs640249A/C polymorphism affects the binding of transcriptional factors in the promoter regions of the ACTC1 gene. Confirmation of the detected association on a larger independent replication cohort will be useful. Conclusions: Genetic variations at the ACTC1 gene may contribute to progression to chronic Chagas Cardiomyopathy among T. cruzi-infected patients, possibly by modulating transcription factor binding to ACTC1 promoter regions.
conferenceObject Quality of life and physical capacity after long-term right ventricular pacing in young adults with congenital atrioventricular block(2012) SILVA, K. R.; COSTA, R.; OLIVEIRA JR., R. M.; MARTINELLI FILHO, M.; LACERDA, M. S.; HUANG, A.; ROSSI, M. B.; MATHIAS JR., W.; PIETROBON, R.; STOLF, N. A. G.Background: Although several studies have demonstrated the deleterious consequences of chronic right ventricular (RV) pacing on ventricular function and synchronicity, its effects on health-related quality of life (HRQL) and physical capacity remains uncertain. Objectives: To evaluate the effect of RV pacing on HRQL and physical capacity of children and young adults with congenital complete atrioventricular (AV) block. Methods: Fifty consecutive patients with permanent RV cardiac pacing due to congenital AV block and under clinical follow-up for more than one year were enrolled. Multidimensional HRQL was assessed with the Short Form-36 Health Survey (SF-36) and Child Health Questionnaire (CHQ-PF50). Physical capacity was tested by the 6-minute walk distance test (6MWD). The scores for each domain and the distance performed at the 6MWD test were compared with demographic and clinical characteristics of patients, using the Student’s t-test and Qui-squaretest. Results: Domains presenting lower scores were Vitality (63.0±20.6), Pain(66.5±25.1) and Mental Health (67.3±20.4) in the SF-36 questionnaire; General Health Perceptions (64.0±15.0) and Parental Impact-Emotional (69.0±30.0) in the CHQ-PF50. Female gender (P=0.026), DDD pacing mode (0.008) and normal left ventricular ejection fraction (0.002) were associated with higher quality of life scores. The average distance performed at the 6MWD test was 677,2 meters (454,5 to 852,8). The 6MWD showed significant association with age (P=0.004), normal ventricular function (P= 0.031) and the absence of cardiovascular drugs use (P= 0.018). Conclusions: The results of this analysis indicated that chronic RV pacing did not affect the HRQL and physical capacity of young patients. Female gender, DDD pacing, normal ventricular function and the absence of cardiovascular medications were associated with better HRQL scores and with better results at 6MWD test.- Long-Term and Sustained Therapeutic Results of a Specific Promonocyte Cell Formulation in Refractory Angina: ReACT (R) (Refractory Angina Cell Therapy) Clinical Update and Cost-Effective Analysis(2015) HOSSNE JR., Nelson Americo; CRUZ, Eduardo; BUFFOLO, Enio; COIMBRA, Anna Carolina Teixeira de Siqueira Mac Dowell; MACHADO, Janaina; GOLDENBERG, Regina Coeli dos Santos; REGAZZI, Germana; AZEVEDO, Silvia; INVITTI, Adriana Luckow; BRANCO, Joao Nelson Rodrigues; OLIVEIRA, Jose Salvador Rodrigues de; STOLF, Noedir Antonio Groppo; MILLER, Leslie W.; SANBERG, Paul R.Mononuclear stem cells have been studied for their potential in myocardial ischemia. In our previous published article, ReACT (R) phase I/II clinical trial, our results suggest that a certain cell population, promonocytes, directly correlated with the perceived angiogenesis in refractory angina patients. This study is ReACT's clinical update, assessing long-term sustained efficacy. The ReACT phase HAM noncontrolled, open-label, clinical trial enrolled 14 patients with refractory angina and viable ischemic myocardium, without ventricular dysfunction, who were not suitable for myocardial revascularization. The procedure consisted of direct myocardial injection of a specific mononuclear cell formulation, with a certain percentage of promonocytes, in a single series of multiple injections (24-90; 0.2 ml each) into specific areas of the left ventricle. Primary endpoints were Canadian Cardiovascular Society Angina Classification (CCSAC) improvement at the 12-month follow-up and ischemic area reduction (scintigraphic analysis) at the 12-month follow-up, in correlation with ReACT's formulation. A recovery index (for patients with more than 1 year follow-up) was created to evaluate CCSAC over time, until April 2011. Almost all patients presented progressive improvement in CCSAC beginning 3 months (p =0.002) postprocedure, which was sustained at the 12-month follow-up (p =0.002), as well as objective myocardium ischemic area reduction at 6 months (decrease of 15%, p <0.024) and 12 months (decrease of 100%, p <0.004) The recovery index (n=10) showed that the patients were graded less than CCSAC 4 for 73.9 +/- 24.2% over a median follow-up time of 46.8 months. After characterization, ReACT's promonocyte concentration suggested a positive correlation with CCSAC improvement (r=-0.575, p =0.082). Quality of life (SF-36 questionnaire) improved significantly in almost all domains. Cost-effectiveness analysis showed decrease in angina-related direct costs. Refractory angina patients presented a sustained long-term improvement in CCSAC and myocardium ischemic areas after the procedure. The long-term follow-up and strong improvement in quality of life reinforce effectiveness. Promonocytes may play a key role in myocardial neoangiogenesis. ReACT dramatically decreased direct costs.
- Geraldo Verginelli, the search for elegance and perfectionism in cardiovascular surgery(2015) STOLF, Noedir A. G.; BRAILE, Domingo M.
bookPart Introdução à semiologia cardiovascular(2013) MOFFA, Paulo Jorge; SANCHES, Paulo César; STOLF, Noedir Antonio Groppo- Influential Factors on the Evaluation of Adamkiewicz Artery Using a 320-Detector Row Computed Tomography Device(2017) AMATO, Alexandre C. M.; PARGA FILHO, Jose R.; STOLF, Noedir A. G.Background: Understanding the difference of Adamkiewicz artery (AKA) presentation in healthy and diseased subjects, and the influence of atherosclerotic factors prevalent in aortic disease patients, are important for aortic disease therapeutic planning. This study used a 320-detector row computed tomography (CT) device to examine the impact of clinical aspects of AKA identification in individuals with and without aortic disease. Methods: Angio-CTs obtained from 115 patients were assessed and the individuals grouped according to the presence or absence of aortic disease. Datasets were analyzed using OsiriX software, and AKA was identified by three-dimensional multiplanar reconstruction. Results: The group without aortic disease (Group A) comprised 32 (52.5%) men and 29 women, with a mean age of 53.7 +/- 16.8 years. The group with aortic disease (Group B) comprised 31 (57.4%) men and 23 women, with a mean age of 64.8 +/- 11.6 years. AKA was identified in 49 (80.3%) participants of Group A and 23 (42.6%) individuals of Group B (P <= 0.0001). In 53 cases (73.6%), AKA originated on the left side. AKA was mainly detected on the left side (73.6%), at the level of T10 to T12 (70%). Tobacco smokers, former smokers, and hypertensive patients had increased odds of having undetected AKA. Conclusions: Using the method described and a state of the art 320-detector row CT device, AKA was detected more frequently among individuals without aortic disease. Thus, aortic disease and atherosclerotic risk factors hindered AKA detection.
- Treatment of rabbits with atherosclerosis induced by cholesterol feeding with daunorubicin associated to a lipid core nanoparticle (LDE)(2023) ALBUQUERQUE, Camila Inagaki; TAVARES, Elaine Rufo; GUIDO, Maria Carolina; CARVALHO, Priscila Oliveira; TAVONI, Thauany Martins; LOPES, Natalia Menezes; SILVA, Bruna Miranda de Oliveira; JENSEN, Leonardo; STOLF, Noedir Antonio Groppo; MARANHA, Raul CavalcanteAtherosclerosis is a cell-proliferative, chronic inflammatory process. The aim was to investigate whether lipid core nanoparticles (LDE) carrying the anti-cancer agent daunorubicin could have anti-atherosclerotic effects. LDE is taken-up by cellular lipoprotein receptors and is capable of concentrating incorporated drugs in inflammed tissues. New Zealand male rabbits were fed 1% cholesterol diet for 8 weeks. Then, animals were treated with LDE-daunorubicin (6 mg/kg/week, IV, n = 9) or with LDE only (n = 7). Atherosclerotic lesions in LDE-daunorubicin group were 50% smaller than in LDE group. In LDE-daunorubicin, protein expressions of the pro-inflammatory markers CD68, TNF-alpha IL-6 and gene expression MCP-1 were lower than in LDE. Gene expression of IL-1 beta, IL-18 and IL-10 were similar. Protein expressions of VEGF and of pro-apoptotic caspase 3, caspase 9 and BAX, and both protein and gene expressions of VCAM-1 were all lower in LDE-daunorubicin. Gene expression of MMP-12 and protein expression of MMP-2 were lower in LDE-daunorubicin, but MMP-9 was not different. Daunorubicin is known as cardiotoxic, but at echocardiography, LDE-daunorubicin had no differences in arch aorta diameters, systolic and diastolic function and in cardiac hypertrophy compared to LDE group. LDEdaunorubicin was capable of reducing atherosclerotic lesions by different mechanisms without observable toxicities.
- Correlation of Bacterial Coinfection Versus Matrix Metalloproteinase 9 and Tissue Inhibitor of Metalloproteinase 1 Expression in Aortic Aneurysm and Atherosclerosis(2013) ROGGERIO, Alessandra; SAMBIASE, Nadia Vieira; PALOMINO, Suely A. P.; CASTRO, Maria Alice Pedreira de; SILVA, Erasmo Simao da; STOLF, Noedir G.; HIGUCHI, Maria de LourdesBackground: We searched for any relationship between Chlamydophila pneumoniae, Mycoplasma pneumoniae, matrix metalloproteinase 9 (MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1) in aneurysmatic atherosclerotic lesions, and whether this relationship differed from that in atherosclerotic nonaneurysmatic lesions. Methods: Twenty-eight tissue samples paired by age and sex were grouped as follows: group 1 included 14 nonaneurysmal atherosclerotic fragments obtained from abdominal aortas collected from necropsies; group 2 included 14 aneurysmatic atherosclerotic aortic fragments obtained from patients during corrective surgery. Immunohistochemistry reactions were evaluated for C pneumoniae, M pneumoniae, MMP-9, and TIMP-1 antigens. Both groups were compared using the Mann-Whitney test, and the correlations among variables were obtained using the Spearman correlation test. P <= 0.05 was considered statistically significant. Results: C pneumoniae and M pneumoniae antigens were detected in 100% of cases. A higher amount of C pneumoniae (P = 0.005), M pneumoniae (P = 0.002), and MMP-9 (P = 0.021) was found in adventitia of group 2 with aneurysm. A positive correlation was found in the aneurysm group, as follows: intima C pneumoniae versus adventitia thickness (r = 0.70; P = 0.01), media C pneumoniae versus adventitia C pneumoniae (r = 0.75; P 0.002), intima C pneumoniae versus media C pneumoniae (r = 0.8; P = 0.00), and adventitia C pneumoniae versus intima M pneumoniae (r = 0.54; P = 0.05); negative correlations were as follows: adventitia thickness and adventitia M pneumoniae (r = -0.65; P = 0.01), media MMP-9 and media thickness (r = -0.55; P = 0.04), TIMP-1 media versus adventitia C pneumoniae (r = -0.86; P = 0.00), and TIMP-1 media versus M pneumoniae intima (r = -0.67; P = 0.03). Nonaneurysmal atherosclerotic group 1 results are as follows: adventitia C pneumoniae versus TIMP-1 media (r = 0.75; P = 0.01) and media C pneumoniae and adventitia C pneumoniae (r = 0.59; P = 0.03). Conclusions: The present work favors a role for coinfection of both M pneumoniae and C pneumoniae in the development of aortic atherosclerotic aneurysm, with increased adventitial inflammation, inhibition of TIMP-1 activity, and increased collagen degradation.
bookPart Abordagem do Paciente com Cardiopatia Presumida ou Estabelecida(2013) MOFFA, Paulo Jorge; SANCHES, Paulo César Ribeiro; STOLF, Noedir Antonio Groppo- History of Heart Transplantation: a Hard and Glorious Journey(2017) STOLF, Noedir A. G.