JOSE EDUARDO KRIEGER
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Cardio-Pneumologia, Faculdade de Medicina - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
73 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 73
- Different Transcriptomic Response to T. cruzi Infection in hiPSC-Derived Cardiomyocytes From Chagas Disease Patients With and Without Chronic Cardiomyopathy(2022) OLIVEIRA, Theo G. M.; VENTURINI, Gabriela; ALVIM, Juliana M.; FEIJO, Larissa L.; DINARDO, Carla L.; SABINO, Ester C.; SEIDMAN, Jonathan G.; SEIDMAN, Christine E.; KRIEGER, Jose E.; PEREIRA, Alexandre C.Chagas disease is a tropical zoonosis caused by Trypanosoma cruzi. After infection, the host present an acute phase, usually asymptomatic, in which an extensive parasite proliferation and intense innate immune activity occurs, followed by a chronic phase, characterized by low parasitemia and development of specific immunity. Most individuals in the chronic phase remain without symptoms or organ damage, a state called indeterminate IND form. However, 20 to 40% of individuals develop cardiac or gastrointestinal complications at any time in life. Cardiomyocytes have an important role in the development of Chronic Chagas Cardiomyopathy (CCC) due to transcriptional and metabolic alterations that are crucial for the parasite survival and replication. However, it still not clear why some infected individuals progress to a cardiomyopathy phase, while others remain asymptomatic. In this work, we used hiPSCs-derived cardiomyocytes (hiPSC-CM) to investigate patterns of infection, proliferation and transcriptional response in IND and CCC patients. Our data show that T. cruzi infection and proliferation efficiency do not differ significantly in PBMCs and hiPSC-CM from both groups. However, RNA-seq analysis in hiPSC-CM infected for 24 hours showed a significantly different transcriptional response to the parasite in cells from IND or CCC patients. Cardiomyocytes from IND showed significant differences in the expression of genes related to antigen processing and presentation, as well as, immune co-stimulatory molecules. Furthermore, the downregulation of collagen production genes and extracellular matrix components was significantly different in these cells. Cardiomyocytes from CCC, in turn, showed increased expression of mTORC1 pathway and unfolded protein response genes, both associated to increased intracellular ROS production. These data point to a differential pattern of response, determined by baseline genetic differences between groups, which may have an impact on the development of a chronic outcome with or without the presentation of cardiac symptoms.
conferenceObject PREDICTORS OF CORONARY ARTERY CALCIFICATION INCIDENCE IN SEVERE HYPERCHOLESTEROLEMIA(2023) MARTE, Ana; MINAME, Marcio Hiroshi; PARDI, Estevao Magalhaes; GANEM, Lucas; MIZUTA, Marjorie Hayashida; ROCHA, Viviane Zorzanelli; PEREIRA, Alexandre Costa; KRIEGER, Jose Eduardo; SANTOS, Raul- Temporal Change of Extracellular Matrix during Vein Arterialization Remodeling in Rats(2019) MIYAKAWA, Ayumi Aurea; BASSANEZE, Vinicius; DUARTE, Nubia Esteban; GIRAO-SILVA, Thais; BIZERRA, Monica Nunes; CAMPOS, Julliana Carvalho; KRIEGER, Jose EduardoThe global expression profile of the arterialized rat jugular vein was established to identify candidate genes and cellular pathways underlying the remodeling process. The arterialized jugular vein was analyzed on days 3 and 28 post-surgery and compared with the normal jugular vein and carotid artery. A gene array platform detected 9846 genes in all samples. A heatmap analysis uncovered patterns of gene expression showing that the arterialized vein underwent a partial transition from vein to artery from day 3 to 28 post-surgery. The same pattern was verified for 1845 key differentially expressed genes by performing a pairwise comparison of the jugular vein with the other groups. Interestingly, hierarchical clustering of 60 genes with altered expression on day 3 and day 28 displayed an expression pattern similar to that of the carotid artery. Enrichment analysis results and the network relationship among genes modulated during vein arterialization showed that collagen might play a role in the early remodeling process. Indeed, the total collagen content was increased, with the augmented expression of collagen I, collagen IV, and collagen V in arterialized veins. Additionally, there was an increase in the expression of versican and Thy-1 and a decrease in the expression of biglycan and beta 1-integrin. Overall, we provide evidence that vein arterialization remodeling is accompanied by consistent patterns of gene expression and that collagen may be an essential element underlying extracellular matrix changes that support the increased vascular wall stress of the new hemodynamic environment.
- Non-HFE hemochromatosis(2012) SANTOS, Paulo Caleb Júnior de Lima; DINARDO, Carla Luana; CANÇADO, Rodolfo Delfini; SCHETTERT, Isolmar Tadeu; KRIEGER, José Eduardo; PEREIRA, Alexandre CostaHereditary hemochromatosis (HH) is an autosomal recessive disorder classically related to HFE mutations. However, since 1996, it is known that HFE mutations explain about 80% of HH cases, with the remaining around 20% denominated non-HFE hemochromatosis. Nowadays, four main genes are implicated in the pathophysiology of clinical syndromes classified as non-HFE hemochromatosis: hemojuvelin (HJV, type 2Ajuvenile HH), hepcidin (HAMP, type 2B juvenile HH), transferrin receptor 2 (TFR2, type 3 HH) and ferroportin (SLC40A1, type 4 HH). The aim of this review is to explore molecular, clinical and management aspects of non-HFE hemochromatosis.
- Impact of diabetes mellitus on arterial stiffness in a representative sample of an urban Brazilian population(2013) ALVIM, Rafael de Oliveira; SANTOS, Paulo Caleb Junior Lima; MUSSO, Mariane Manso; CUNHA, Roberto de Sa; KRIEGER, Jose Eduardo; MILL, Jose Geraldo; PEREIRA, Alexandre CostaBackground: Independent of other cardiovascular (CV) risk factors, increased arterial stiffness has been established as a predictor of morbidity and mortality. The main aim of this study was to investigate the impact of diabetes on arterial stiffness in a representative sample of an urban Brazilian population plus Amerindians. Methods: A total of 1,415 individuals from the general population were randomly selected plus 588 Amerindians from a native community in Brazil. In addition, a sub-sample of 380 individuals from the general population had 5-year follow-up data. Pulse wave velocity (PWV) was measured with a non-invasive automatic device (Complior, Colson; Garges les Gonesses, France) and increased arterial stiffness was defined as PWV >= 12 m/s. Results: In the overall group, diabetic individuals had higher frequencies of increased arterial stiffness and hypertension. They also had higher values of PWV, body mass index, total cholesterol, triglycerides, systolic and diastolic blood pressures compared to non-diabetic individuals (p < 0.01). In an analysis stratified by hypertension, PWV values and increased arterial stiffness frequency were higher in diabetic individuals in both groups (hypertensive and non-hypertensive) (p < 0.05). Furthermore, higher risk for increased arterial stiffness was observed in the diabetic individuals from the overall group (OR = 2.27; CI = 1.47-3.52, p < 0.001) and from the hypertensive group (OR = 2.70; CI = 1.58-4.75, p < 0.001), adjusted for covariates. Regarding the ethnic stratification, diabetic individuals from Amerindian, White, and Mulatto (mixed-race) groups had higher PWV values and a greater frequency of increased arterial stiffness compared to non-diabetic individuals. Both diabetic and non-diabetic individuals had higher PWV values after 5 years. There was no significant difference in the 5-year PWV progression in diabetic compared to non-diabetic individuals. Conclusions: These results confirm, in a sample of Brazilian population, that the presence of diabetes is associated with increased arterial stiffness and it may contribute in part to increased cardiovascular risk in diabetic patients.
- MTRR rs326119 polymorphism is associated with plasma concentrations of homocysteine and cobalamin, but not with congenital heart disease or coronary atherosclerosis in Brazilian patients(2017) HORITA, Melanie; BUENO, Carolina Tosin; HORIMOTO, Andrea R.; LEMOS, Pedro A.; MORANDINI-FILHO, Antonio A.; KRIEGER, Jose E.; SANTOS, Paulo C. J. L.; PEREIRA, Alexandre C.Background: Differences in the distribution of the MTRR rs326119 polymorphism (c.56+ 781 A>C) between patients with congenital heart disease (CHD) and controls have been described in Chinese individuals. The association is thought to be due to deregulation of homocysteine-cobalamin pathways. This has not been replicated in other populations. The primary objective of this study was to assess the influence of the MTRR rs326119 polymorphism on biochemical parameters of vitamin B12 metabolism, coronary lesions, and congenital heart disease in Brazilian subjects. Methods: We selected 722 patients with CHD, 1432 patients who underwent coronary angiography, and 156 blood donors. Genotyping for the MTRR polymorphism was evaluated by high-resolution melting analysis, and biochemical tests of vitamin B12 metabolism were measured. Results: Subjects carrying the AC or CC genotypes had higher homocysteine concentrations (9.7 +/- 0.4 mu mol/L and 10.1 +/- 0.6 mu mol/L) and lower cobalamin concentrations (260.5 +/- 13.3 pmol/L and 275.6 +/- 19.9 pmol/L) compared with the subjects carrying the AA genotype (8.7 +/- 0.5 mu mol/L and 304.8 +/- 14.7 pmol/L), respectively. A multiple linear regression model also identified a significant association between the number of C variant alleles with the concentrations of homocysteine and cobalamin. Nonetheless, the allelic and genotypic distributions for MTRR rs326119 were not associated with CHD or coronary atherosclerosis in the studied samples. Conclusion: Our findings indicate that the MTRR rs326119 variant might be a genetic marker associated with homocysteine and cobalamin concentrations, but not a strong risk factor for CHD or coronary atherosclerosis in the Brazilian population. (C) 2016 The Authors.
conferenceObject Fully Automated Quantification of Cardiac Indices from Cine MRI Using a Combination of Convolution Neural Networks(2020) PEREIRA, Renato F.; REBELO, Marina S.; MORENO, Ramon A.; MARCO, Anderson G.; LIMA, Daniel M.; ARRUDA, Marcelo A. F.; KRIEGER, Jose E.; GUTIERREZ, Marco A.Cardiovascular magnetic resonance imaging (CMRI) is one of the most accurate non-invasive modalities for evaluation of cardiac function, especially the left ventricle (LV). In this modality, the manual or semi-automatic delineation of LV by experts is currently the standard clinical practice for chambers segmentation. Despite these efforts, global quantification of LV remains a challenge. In this work, a combination of two convolutional neural network (CNN) architectures for quantitative evaluation of the LV is described, which estimates the cavity and the myocardium areas, endocardial cavity dimensions in three directions, and the myocardium regional wall thickness in six radial directions. The method was validated in CMRI exams of 56 patients (LVQuan19 dataset) and evaluated by metrics Dice Index, Mean Absolute Error, and Correlation with superior performance compared to the state-of-the-art methods. The combination of the CNN architectures provided a simpler yet fully automated approach, requiring no specialist interaction.- Trypanosoma cruzi cardiomyocyte infection promotes innate immune response and metabolic rewiring(2022) VENTURINI, Gabriela; ALVIM, Juliana; PADILHA, Kallyandra; TOEPFER, Christopher; GORHAM, Joshua; BIAGI, Diogo; SCHENKMAN, Sergio; CARVALHO, Valdemir; SALGUEIRO, Jessica; CARDOZO, Karina; KRIEGER, Jose; PEREIRA, Alexandre; SEIDMAN, Jonathan; SEIDMAN, Christine
- CardioBERTpt: Transformer-based Models for Cardiology Language Representation in Portuguese(2023) SCHNEIDER, Elisa Terumi Rubel; GUMIEL, Yohan Bonescki; SOUZA, Joao Vitor Andrioli de; MUKAI, Lilian Mie; OLIVEIRA, Lucas Emanuel Silva e; REBELO, Marina de Sa; GUTIERREZ, Marco Antonio; KRIEGER, Jose Eduardo; TEODORO, Douglas; MORO, Claudia; PARAISO, Emerson CabreraContextual word embeddings and the Transformers architecture have reached state-of-the-art results in many natural language processing (NLP) tasks and improved the adaptation of models for multiple domains. Despite the improvement in the reuse and construction of models, few resources are still developed for the Portuguese language, especially in the health domain. Furthermore, the clinical models available for the language are not representative enough for all medical specialties. This work explores deep contextual embedding models for the Portuguese language to support clinical NLP tasks. We transferred learned information from electronic health records of a Brazilian tertiary hospital specialized in cardiology diseases and pre-trained multiple clinical BERT-based models. We evaluated the performance of these models in named entity recognition experiments, fine-tuning them in two annotated corpora containing clinical narratives. Our pre-trained models outperformed previous multilingual and Portuguese BERT-based models for cardiology and multi-specialty environments, reaching the state-of-the-art for analyzed corpora, with 5.5% F1 score improvement in TempClinBr (all entities) and 1.7% in SemClinBr (Disorder entity) corpora. Hence, we demonstrate that data representativeness and a high volume of training data can improve the results for clinical tasks, aligned with results for other languages.
- Cardiovascular disease onset in old people with severe hypercholesterolemia(2023) COUTINHO, Elaine R.; MINAME, Marcio H.; ROCHA, Viviane Z.; BITTENCOURT, Marcio S.; JANNES, Cinthia E.; KRIEGER, Jose E.; PEREIRA, Alexandre C.; SANTOS, Raul D.Background and aims: Familial hypercholesterolemia (FH) variants are associated with higher atherosclerotic cardiovascular disease risk (ASCVD) even when compared with other forms of severe hypercholesterolemia, especially in young people. Lipid lowering therapies (LLT) may change hypercholesterolemia natural history. This study aimed at evaluating factors associated with occurrence of ASCVD in old severe hypercholesterolemics diagnosed or not with FH and undergoing LLT.Methods: Hypercholesterolemic individuals >= 60 years participating on a genetic cascade screening for FH were divided in 4 groups (2 x 2) according to the presence (variant+) or not (variant-) of FH genetic variants and previous ASCVD (ASCVD+ and ASCVD-). Biomarkers associated with new incident ASCVD events were tested using Cox models. Continuous data shown as medians (%25; %75).Results: From 4,111 genotyped individuals, 377 (9.1%) were elderly [age 66 (63; 71) years], 28.9% males, 42.7% variant+, 32.1% with previous ASCVD, LLT duration 9 (5; 16) years, and on treatment LDL-cholesterol 144 (109; 200) mg/dL. After 4.8 (7; 3) years of follow up there were 47 incident events (12.4%, 2.7% patient/year). The annualized event rates were 0.8% (95% CI 0.36%; 1.70%), 2.3% (95% CI 1.3%; 4.1%), 5.2% (95% CI 2.8%; 9.7%) and 6.3% (95% CI 4.0%; 10.0%) respectively for groups variant-/ASCVD-, variant+/ASCVD-, variant-/ ASCVD+ and, variant+/ASCVD+ (p log rank p < 0.001). Only presence of previous ASCVD was independently associated with incident ASCVD [hazard ratio 3.236 (95%CI 1.497-6.993, p = 0.003)]. No interaction was found for previous ASCVD and variants.Conclusions: In old severe hypercholesterolemic individuals undergoing long-term LLT previous ASCVD was associated with incident events while FH causing variants were not.