MARIANA LOMBARDI PERES DE CARVALHO
Índice h a partir de 2011
2
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina
7 resultados
Resultados de Busca
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- Time-regulated transcripts with the potential to modulate human pluripotent stem cell-derived cardiomyocyte differentiation(2022) MUNOZ, Juan J. A. M.; DARIOLLI, Rafael; SILVA, Caio Mateus da; NERI, Elida A.; VALADAO, Iuri C.; TURACA, Lauro Thiago; LIMA, Vanessa M.; CARVALHO, Mariana Lombardi Peres de; VELHO, Mariliza R.; SOBIE, Eric A.; KRIEGER, Jose E.Background Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a promising disease model, even though hiPSC-CMs cultured for extended periods display an undifferentiated transcriptional landscape. MiRNA-target gene interactions contribute to fine-tuning the genetic program governing cardiac maturation and may uncover critical pathways to be targeted. Methods We analyzed a hiPSC-CM public dataset to identify time-regulated miRNA-target gene interactions based on three logical steps of filtering. We validated this process in silico using 14 human and mouse public datasets, and further confirmed the findings by sampling seven time points over a 30-day protocol with a hiPSC-CM clone developed in our laboratory. We then added miRNA mimics from the top eight miRNAs candidates in three cell clones in two different moments of cardiac specification and maturation to assess their impact on differentiation characteristics including proliferation, sarcomere structure, contractility, and calcium handling. Results We uncovered 324 interactions among 29 differentially expressed genes and 51 miRNAs from 20,543 transcripts through 120 days of hiPSC-CM differentiation and selected 16 genes and 25 miRNAs based on the inverse pattern of expression (Pearson R-values < - 0.5) and consistency in different datasets. We validated 16 inverse interactions among eight genes and 12 miRNAs (Person R-values < - 0.5) during hiPSC-CMs differentiation and used miRNAs mimics to verify proliferation, structural and functional features related to maturation. We also demonstrated that miR-124 affects Ca2+ handling altering features associated with hiPSC-CMs maturation. Conclusion We uncovered time-regulated transcripts influencing pathways affecting cardiac differentiation/maturation axis and showed that the top-scoring miRNAs indeed affect primarily structural features highlighting their role in the hiPSC-CM maturation.
conferenceObject Atrial fibrillation as a cornerstone of laminopathy(2018) CALIL, Z. O.; PESSENTE, G. A.; SACILOTTO, L.; OLIVETTI, N. Q. S.; HACHUL, D. T.; WU, T. C.; GRUPPI, C. J.; CARVALHO, M. L. P.; ARANHA, A. F.; PEDROSA, A. A. A.; HARDY, C. A.; PISANI, C. F.; PEREIRA, A. C.; SCANAVACCA, M. I.; DARRIEUX, F. C. C.- Clinical Features, Genetic Findings, and Risk Stratification in Arrhythmogenic Right Ventricular Cardiomyopathy: Data From a Brazilian Cohort(2023) OLIVETTI, Natalia Sangiorgi; SACILOTTO, Luciana; WULKAN, Fanny; PESSENTE, Gabrielle D'Arezzo; CARVALHO, Mariana Lombardi Peres de; MOLETA, Danilo; HACHUL, Denise Tessariol; VERONESE, Pedro; HARDY, Carina; PISANI, Cristiano; WU, Tan Chen; VIEIRA, Marcelo Luiz Campos; FRANCA, Lucas Arraes de; FREITAS, Matheus de Souza; ROCHITTE, Carlos Eduardo; BUENO, Savia Christina; LOVISI, Vitor Bastos; KRIEGER, Jose Eduardo; SCANAVACCA, Mauricio; PEREIRA, Alexandre da Costa; DARRIEUX, Francisco da CostaBackground:Arrhythmogenic right ventricular cardiomyopathy (ARVC), a rare inherited disease, causes ventricular tachycardia, sudden cardiac death, and heart failure (HF). We investigated ARVC clinical features, genetic findings, natural history, and the occurrence of life-threatening arrhythmic events (LTAEs), HF death, or heart transplantation (HF-death/HTx) to identify risk factors. Methods:The clinical course of 111 consecutive patients with definite ARVC, predictors of LTAE, HF-death/HTx, and combined events were analyzed in the entire cohort and in a subgroup of 40 patients without sustained ventricular arrhythmia before diagnosis. Results:The 5-year cumulative probability of LTAE was 30% and HF-death/HTx was 10%. Predictors of HF-death/HTx were reduced right ventricle ejection fraction (HR: 0.93; P=0.010), HF symptoms (HR: 4.37; P=0.010), epsilon wave (HR: 4.99; P=0.015), and number of leads with low QRS voltage (HR: 1.28; P=0.001). Each additional lead with low QRS voltage increased the risk of HF-death/HTx by 28%. Predictors of LTAE were prior syncope (HR: 1.81; P=0.040), number of leads with T wave inversion (HR: 1.17; P=0.039), low QRS voltage (HR: 1.12; P=0.021), younger age (HR: 0.97; P=0.006), and prior ventricular arrhythmia/ventricular fibrillation (HR: 2.45; P=0.012). Each additional lead with low QRS voltage increased the risk of LTAE by 17%. In patients without ventricular arrhythmia before clinical diagnosis of ARVC, the number of leads with low QRS voltage (HR: 1.68; P=0.023) was independently associated with HF-death/HTx. Conclusions:Our study demonstrated the characteristics of a specific cohort with a high prevalence of arrhythmic burden at presentation, male predominance, younger age and HF severe outcomes. Our main results suggest that the presence and extension of low QRS voltage can be a risk predictor for HF-death/HTx in ARVC patients, regardless of the arrhythmic risk. This study can contribute to the global ARVC risk stratification, adding new insights to the international current scientific knowledge.
- Mexiletine in a Newborn with Type 3 Long QT Syndrome: When Access is Difficult(2022) PEREIRA, Eduardo Nolla Silva; SACILOTTO, Luciana; PESSENTE, Gabrielle D'Arezzo; GUIRAO, Cinthya; CARVALHO, Mariana Lombardi Peres de; PEREIRA, Alexandre da Costa; DARRIEUX, Francisco Carlos da Costa; SCANAVACCA, Mauricio Ibrahim
- SMIM1 intron 2 gene variations leading to variability in Vel antigen expression among Brazilian blood donors(2019) DEZAN, Marcia Regina; COSTA-NETO, Abel; GOMES, Carolina Nunes; RIBEIRO, Ingrid Helena; OLIVEIRA, Valeria Brito; V, Marina C. A. Conrado; OLIVEIRA, Theo Gremen M.; CARVALHO, Mariana L. P.; ARANHA, Aline Fernanda; BOSI, Silvia R. A.; SALLES, Nanci A.; KRIEGER, Jose Eduardo; PEREIRA, Alexandre Costa; SABINO, Ester Cerdeira; ROCHA, Vanderson; MENDRONE-JUNIOR, Alfredo; DINARDO, Carla Luana; LEVI, Jose EduardoBackground: There is a significant inter-individual heterogeneity of Vel antigen expression which can lead to inaccuracies on Vel phenotyping of blood donors and, potentially, to hemolytic post-transfusion reactions. Our aim was to evaluate the impact of genetic variants in the SMIM1 intron 2 on the expression of Vel antigen among Brazilian blood donors harboring the c.64_80del17 deletion in heterozygosity. Methods: Donors presenting the SMIM1 c.64_80del17 in heterozygosity were included in the study and subjected to SMIM1 intron 2 direct sequencing aiming to genotype the following polymorphisms: rs143702418, rs1181893, rs191041962, rs6673829, rs1175550 and rs9424296. Results: SMIM1 intron 2 sequencing was performed on two hundred donors presenting one c.64_80del17 allele. The rs1175550 polymorphism significantly impacted on Vel antigen expression. Variations in the strength of agglutination on Vel phenotyping were also observed according to the rs6673829 genotype, but this difference did not persist with statistical relevance after multivariate analysis. Conclusion: The presence of the rs1175550A allele of SMIM1 is significantly and independently associated with a decrease in Vel antigen expression. Even though the population in Brazil is intensely mixed, the allele frequencies obtained in the current study were very similar to that reported for Europeans.
- Clinical, Laboratory, and Imaging Profile in Patients with Systemic Amyloidosis in a Brazilian Cardiology Referral Center(2022) FERNANDES, Fabio; ALENCAR NETO, Aristoteles Comte de; BUENO, Bruno Vaz Kerges; CAFEZEIRO, Caio Reboucas Fonseca; RISSATO, Joao Henrique; SZOR, Roberta Shcolnik; CARVALHO, Mariana Lombardi Peres de; MATHIAS JUNIOR, Wilson; LINO, Angelina Maria Martins; CASTELLI, Jussara Bianchi; SOUZA, Evandro de Oliveira; RAMIRES, Felix Jose Alvarez; HOTTA, Viviane Tiemi; SOARES JUNIOR, Jose; TAVARES, Caio de Assis Moura; KRIEGER, Jose Eduardo; ROCHITTE, Carlos Eduardo; DABARIAN, Andre; HAJJAR, Ludhmila Abrahao; KALIL FILHO, Roberto; MADY, CharlesBackground: Systemic amyloidosis is a disease with heterogeneous clinical manifestations. Diagnosis depends on clinical suspicion combined with specific complementary methods. Objective: To describe the clinical, laboratory, electrocardiographic, and imaging profile in patients with systemic amyloidosis with cardiac involvement. Methods: This study was conducted with a convenience sample, analyzing clinical, laboratory, electrocardiographic, echocardiographic, nuclear medicine, and magnetic resonance data. Statistical significance was set at p < 0.05. Results: A total of 105 patients were evaluated (median age of 66 years), 62 of whom were male. Of all patients, 83 had transthyretin (ATTR) amyloidosis, and 22 had light chain (AL) amyloidosis. With respect to ATTR cases, 68.7% were the hereditary form (ATTRh), and 31.3% were wild type (ATTRw). The most prevalent mutations were Val142Ile (45.6%) and Val50Met (40.3%). Time from onset of symptoms to diagnosis was 0.54 and 2.15 years, in the AL and ATTR forms, respectively (p < 0.001). Cardiac involvement was observed in 77.9% of patients with ATTR and in 90.9% of those with AL. Alterations were observed in atrioventricular and intraventricular conduction in 20% and 27.6% of patients, respectively, with 33.7% in ATTR and 4.5% in AL (p = 0.006). In the ATTRw form, there were more atrial arrhythmias than in ATTRh (61.5% versus 22.8%; p = 0.001). On echocardiogram, median septum thickness in ATTRw, ATTRh, and AL was 15 mm, 12 mm, and 11 mm, respectively (p = 0.193). Elevated BNP was observed in 89.5% of patients (median 249, ICR 597.7), and elevated troponin was observed in 43.2%. Conclusion: In this setting, it was possible to characterize cardiac involvement in systemic amyloidosis in its different subtypes by means of clinical history and the diagnostic methods described.
- Enhancing Arrhythmogenic Right Ventricular Cardiomyopathy Detection and Risk Stratification: Insights from Advanced Echocardiographic Techniques(2024) OLIVETTI, Natalia; SACILOTTO, Luciana; MOLETA, Danilo Bora; FRANCA, Lucas Arraes de; CAPELINE, Lorena Squassante; WULKAN, Fanny; WU, Tan Chen; PESSENTE, Gabriele D'Arezzo; CARVALHO, Mariana Lombardi Peres de; HACHUL, Denise Tessariol; PEREIRA, Alexandre da Costa; KRIEGER, Jose E.; SCANAVACCA, Mauricio Ibrahim; VIEIRA, Marcelo Luiz Campos; DARRIEUX, FranciscoIntroduction: The echocardiographic diagnosis criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC) are highly specific but sensitivity is low, especially in the early stages of the disease. The role of echocardiographic strain in ARVC has not been fully elucidated, although prior studies suggest that it can improve the detection of subtle functional abnormalities. The purposes of the study were to determine whether these advanced measures of right ventricular (RV) dysfunction on echocardiogram, including RV strain, increase diagnostic value for ARVC disease detection and to evaluate the association of echocardiographic parameters with arrhythmic outcomes. Methods: The study included 28 patients from the Heart Institute of S & atilde;o Paulo ARVC cohort with a definite diagnosis of ARVC established according to the 2010 Task Force Criteria. All patients were submitted to ECHO's advanced techniques including RV strain, and the parameters were compared to prior conventional visual ECHO and CMR. Results: In total, 28 patients were enrolled in order to perform ECHO's advanced techniques. A total of 2/28 (7%) patients died due to a cardiovascular cause, 2/28 (7%) underwent heart transplantation, and 14/28 (50%) patients developed sustained ventricular arrhythmic events. Among ECHO's parameters, RV dilatation, measured by RVDd (p = 0.018) and RVOT PSAX (p = 0.044), was significantly associated with arrhythmic outcomes. RV free wall longitudinal strain < 14.35% in absolute value was associated with arrhythmic outcomes (p = 0.033). Conclusion: Our data suggest that ECHO's advanced techniques improve ARVC detection and that abnormal RV strain can be associated with arrhythmic risk stratification. Further studies are necessary to better demonstrate these findings and contribute to risk stratification in ARVC, in addition to other well-known risk markers.