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1.
Int. j. cardiovasc. sci. (Impr.) ; 32(2): 152-157, mar.-abr. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-988204

RESUMO

Background: Galectin-3 is the designation given to the protein that binds to ß-galactosides, expressed by activated macrophages and described as a cardiac fibrosis mediator. In hypertrophic cardiomyopathy (HCM), myocardial fibrosis is an independent predictor of adverse outcome; however, the association between Galectin-3 and myocardial fibrosis has not been studied in this cardiopathy. Objective: To evaluate the association of Galectin-3 and the presence of myocardial fibrosis in a patient with hypertrophic cardiomyopathy. Methods: Galectin-3 was measured in automated equipment using the Elisa technique in 100 participants divided into two groups: 50 patients with hypertrophic cardiomyopathy and 50 healthy control subjects. All patients with hypertrophic cardiomyopathy underwent magnetic nuclear resonance with the late enhancement technique to investigate myocardial fibrosis. For the statistical analysis, p values < 0.05 were considered statistically significant. Results: Galectin-3 levels were low and did not show significant differences between patients with hypertrophic cardiomyopathy and the control group,10.3 ± 3.1 ng/dL and 11.3 ± 2.6 ng/dL (p = 0.12) respectively. Myocardial fibrosis was a common finding and was identified in 84% (42/50) of patients with HCM, but no differences were observed between Galectin-3 levels when comparing patients with and without fibrosis, 10.3 ± 2.4 ng/dL and 10.1 ± 2.1 ng/dL (p = 0.59). Conclusion: The results did not show an association between Galectin-3 and myocardial fibrosis in patients with hypertrophic cardiomyopathy, suggesting that non-inflammatory mechanisms of myocardial fibrosis formation and cardiac remodeling are involved in this cardiopathy


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Galectina 3 , Fibrose Endomiocárdica , Arritmias Cardíacas/diagnóstico , Diagnóstico por Imagem/métodos , Espectroscopia de Ressonância Magnética/métodos , Biomarcadores , Doenças Cardiovasculares/diagnóstico , Ecocardiografia Doppler/métodos , Análise Estatística
2.
Int. j. cardiovasc. sci. (Impr.) ; 32(2): 152-157, mar.-abr. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-989994

RESUMO

Galectin-3 is the designation given to the protein that binds to ß-galactosides, expressed by activated macrophages and described as a cardiac fibrosis mediator. In hypertrophic cardiomyopathy (HCM), myocardial fibrosis is an independent predictor of adverse outcome; however, the association between Galectin-3 and myocardial fibrosis has not been studied in this cardiopathy. Objective: To evaluate the association of Galectin-3 and the presence of myocardial fibrosis in a patient with hypertrophic cardiomyopathy. Methods: Galectin-3 was measured in automated equipment using the Elisa technique in 100 participants divided into two groups: 50 patients with hypertrophic cardiomyopathy and 50 healthy control subjects. All patients with hypertrophic cardiomyopathy underwent magnetic nuclear resonance with the late enhancement technique to investigate myocardial fibrosis. For the statistical analysis, p values < 0.05 were considered statistically significant. Results: Galectin-3 levels were low and did not show significant differences between patients with hypertrophic cardiomyopathy and the control group, 10.3 ± 3.1 ng/dL and 11.3 ± 2.6 ng/dL (p = 0.12) respectively. Myocardial fibrosis was a common finding and was identified in 84% (42/50) of patients with HCM, but no differences were observed between Galectin-3 levels when comparing patients with and without fibrosis, 10.3 ± 2.4 ng/dL and 10.1 ± 2.1 ng/dL (p = 0.59). Conclusion: The results did not show an association between Galectin-3 and myocardial fibrosis in patients with hypertrophic cardiomyopathy, suggesting that non-inflammatory mechanisms of myocardial fibrosis formation and cardiac remodeling are involved in this cardiopathy


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Galectina 3 , Fibrose Endomiocárdica , Arritmias Cardíacas/diagnóstico por imagem , Diagnóstico por Imagem/métodos , Espectroscopia de Ressonância Magnética/métodos , Biomarcadores , Doenças Cardiovasculares/diagnóstico , Ecocardiografia Doppler/métodos , Análise Estatística
3.
Can J Physiol Pharmacol ; 97(2): 140-145, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30557036

RESUMO

Metabolic, inflammatory, and autonomic nervous system (ANS) dysfunction are present in patients with heart failure. However, whether these changes are due to left ventricular dysfunction or heart failure etiology is unknown. We evaluated metabolism and inflammatory activity in patients with idiopathic dilated cardiomyopathy (IDC) and Chagas cardiomyopathy (CHG) and their correlation with the ANS. Forty-six patients were divided into 3 groups: IDC, CHG, and control. We evaluated adiponectin, leptin, insulin, interleukin-6, and tumor necrosis factor-alpha. ANS were analyzed by heart rate variability in time and frequency domains on a 24-hour Holter monitor. Levels of glucose, cholesterol, leptin, and adiponectin did not show differences between groups. Insulin levels were lower in CHG group (5.4 ± 3.3 µU/mL) when compared with control (8.0 ± 4.9 µU/mL) and IDC (9.9 ± 5.0 µU/mL) groups (p = 0.007). Insulin was positively associated with LFr/HFr ratio (r = 0.562; p = 0.029) and with the LFr component (r = 0.562; p = 0.029) and negatively associated with adiponectin (r = -0.603; p = 0.017) in CHG group. The addition of an adiponectin unit reduced average insulin by 0.332 µg/mL. Insulin levels were decreased in the CHG group when compared with the IDC group and were associated with ANS indexes and adiponectin levels.


Assuntos
Adipocinas/sangue , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Chagásica/metabolismo , Insulina/sangue , Adipocinas/metabolismo , Adulto , Sistema Nervoso Autônomo/fisiopatologia , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Chagásica/sangue , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/fisiopatologia , Ecocardiografia Doppler , Eletrocardiografia , Feminino , Coração , Frequência Cardíaca/fisiologia , Humanos , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade
4.
Artigo em Inglês | MEDLINE | ID: mdl-30519544

RESUMO

Background: Archaeal genes present in Trypanosoma cruzi may represent symbionts that would explain development of heart failure in 30% of Chagas disease patients. Extracellular vesicles in peripheral blood, called exosomes (< 0.1 µm) or microvesicles (>0.1 µm), present in larger numbers in heart failure, were analyzed to determine whether they are derived from archaea in heart failure Chagas disease. Methods: Exosomes and microvesicles in serum supernatant from 3 groups were analyzed: heart failure Chagas disease (N = 26), asymptomatic indeterminate form (N = 21) and healthy non-chagasic control (N = 16). Samples were quantified with transmission electron microscopy, flow cytometer immunolabeled with anti-archaemetzincin-1 antibody (AMZ 1, archaea collagenase) and probe anti-archaeal DNA and zymography to determine AMZ1 (Archaeal metalloproteinase) activity. Results: Indeterminate form patients had higher median numbers of exosomes/case vs. heart failure patients (58.5 vs. 25.5, P < 0.001), higher exosome content of AMZ1 antigens (2.0 vs. 0.0; P < 0.001), and lower archaeal DNA content (0.2 vs. 1.5, P = 0.02). A positive correlation between exosomes and AMZ1 content was seen in indeterminate form (r = 0.5, P < 0.001), but not in heart failure patients (r = 0.002, P = 0.98). Higher free archaeal DNA (63.0 vs. 11.1, P < 0.001) in correlation with exosome numbers (r = 0.66, P = 0.01) was seen in heart failure but not in indeterminate form (r = 0.29, P = 0.10). Flow cytometer showed higher numbers of AMZ1 microvesicles in indeterminate form (64 vs. 36, P = 0.02) and higher archaeal DNA microvesicles in heart failure (8.1 vs. 0.9, P < 0.001). Zymography showed strong% collagenase activity in HF group, mild activity in IF compared to non-chagasic healthy group (121 ± 14, 106 ± 13 and 100; P < 0.001). Conclusions: Numerous exosomes, possibly removing and degrading abnormal AMZ1 collagenase, are associated with indeterminate form. Archaeal microvesicles and their exosomes, possibly associated with release of archaeal AMZ1 in heart failure, are future candidates of heart failure biomarkers if confirmed in larger series, and the therapeutic focus in the treatment of Chagas disease.


Assuntos
Archaea/fisiologia , Doença de Chagas/imunologia , Insuficiência Cardíaca/imunologia , Trypanosoma cruzi/imunologia , Trypanosoma cruzi/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Bactérias/sangue , Biomarcadores , Doença de Chagas/sangue , Colagenases , Exossomos , Feminino , Citometria de Fluxo , Insuficiência Cardíaca/sangue , Humanos , Masculino , Metaloproteases , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade
5.
Arq. bras. cardiol ; 105(1): 28-36, July 2015. tab
Artigo em Inglês | LILACS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: lil-755004

RESUMO

Background:

Chagas disease is a cause of dilated cardiomyopathy, and information about left atrial (LA) function in this disease still lacks.

Objective:

To assess the different LA functions (reservoir, conduit and pump functions) and their correlation with the echocardiographic parameters of left ventricular (LV) systolic and diastolic functions.

Methods:

10 control subjects (CG), and patients with Chagas disease as follows: 26 with the indeterminate form (GI); 30 with ECG alterations (GII); and 19 with LV dysfunction (GIII). All patients underwent M-mode and two-dimensional echocardiography, pulsed-wave Doppler and tissue Doppler imaging.

Results:

Reservoir function (Total Emptying Fraction: TEF): (p <0.0001), lower in GIII as compared to CG (p = 0.003), GI (p <0.001) and GII (p <0.001). Conduit function (Passive Emptying Fraction: PEF): (p = 0.004), lower in GIII (GIII and CG, p = 0.06; GI and GII, p = 0.06; and GII and GIII, p = 0.07). Pump function (Active Emptying Fraction: AEF): (p = 0.0001), lower in GIII as compared to CG (p = 0.05), GI (p<0.0001) and GII (p = 0.002). There was a negative correlation of E/e’average with the reservoir and pump functions (TEF and AEF), and a positive correlation of e’average with s’ wave (both septal and lateral walls) and the reservoir, conduit and pump LA functions.

Conclusion:

An impairment of LA functions in Chagas cardiomyopathy was observed.

.

Fundamento:

A doença de Chagas é uma causa de miocardiopatia dilatada, sendo ainda pouco conhecida a função do átrio esquerdo (AE) nessa doença.

Objetivo:

Avaliar as diferenças nas funções do AE (reservatório, conduto e bomba) e sua correlação com os parâmetros ecocardiográficos das funções sistólica e diastólica do ventrículo esquerdo (VE).

Método:

10 controles (GC) e os seguintes pacientes com doença de Chagas: 26 com a forma indeterminada (GI); 30 com alterações eletrocardiográficas (GII); e 19 com disfunção de VE (GIII). Todos os pacientes foram submetidos a ecocardiografia bidimensional e em modo M, Doppler pulsado e Doppler tecidual.

Resultados:

Função de reservatório (fração de esvaziamento total: FET) (p < 0,0001), mais baixa no GIII do que no GC (p = 0,003), GI (p < 0,001) e GII (p < 0,001). Função de conduto (fração de esvaziamento passivo: FEP) (p = 0,004), mais baixa no GIII (GIII e GC, p = 0.06; GI e GII, p = 0.06; e GII e GIII, p = 0,07). Função de bomba (fração de esvaziamento ativo: FEA) (p = 0,0001), mais baixa no GIII do que no CG (p = 0,05), GI (p<0,0001) e GII (p = 0,002). Observou-se uma correlação negativa entre E/e’média e as funções de reservatório e de bomba (FET e FEA), e uma correlação positiva entre as ondas e’média e s’ (paredes septal e lateral) e as funções de reservatório, conduto e bomba.

Conclusão:

Observou-se comprometimento das funções do AE na miocardiopatia chagásica.

.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Função do Átrio Esquerdo/fisiologia , Cardiomiopatia Chagásica/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Cardiomiopatia Dilatada/fisiopatologia , Estudos de Casos e Controles , Cardiomiopatia Chagásica , Ecocardiografia Doppler , Contração Miocárdica/fisiologia , Valores de Referência , Estatísticas não Paramétricas , Volume Sistólico/fisiologia , Disfunção Ventricular Esquerda
6.
Arq Bras Cardiol ; 105(1): 28-36, 2015 Jul.
Artigo em Inglês, Português | MEDLINE | ID: mdl-25993486

RESUMO

BACKGROUND: Chagas disease is a cause of dilated cardiomyopathy, and information about left atrial (LA) function in this disease still lacks. OBJECTIVE: To assess the different LA functions (reservoir, conduit and pump functions) and their correlation with the echocardiographic parameters of left ventricular (LV) systolic and diastolic functions. METHODS: 10 control subjects (CG), and patients with Chagas disease as follows: 26 with the indeterminate form (GI); 30 with ECG alterations (GII); and 19 with LV dysfunction (GIII). All patients underwent M-mode and two-dimensional echocardiography, pulsed-wave Doppler and tissue Doppler imaging. RESULTS: Reservoir function (Total Emptying Fraction: TEF): (p <0.0001), lower in GIII as compared to CG (p = 0.003), GI (p <0.001) and GII (p <0.001). Conduit function (Passive Emptying Fraction: PEF): (p = 0.004), lower in GIII (GIII and CG, p = 0.06; GI and GII, p = 0.06; and GII and GIII, p = 0.07). Pump function (Active Emptying Fraction: AEF): (p = 0.0001), lower in GIII as compared to CG (p = 0.05), GI (p<0.0001) and GII (p = 0.002). There was a negative correlation of E/e' (average) with the reservoir and pump functions (TEF and AEF), and a positive correlation of e' (average) with s' wave (both septal and lateral walls) and the reservoir, conduit and pump LA functions. CONCLUSION: An impairment of LA functions in Chagas cardiomyopathy was observed.


Assuntos
Função do Átrio Esquerdo/fisiologia , Cardiomiopatia Chagásica/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Adulto , Cardiomiopatia Dilatada/fisiopatologia , Estudos de Casos e Controles , Cardiomiopatia Chagásica/diagnóstico por imagem , Ecocardiografia Doppler , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/fisiologia , Valores de Referência , Estatísticas não Paramétricas , Volume Sistólico/fisiologia , Disfunção Ventricular Esquerda/diagnóstico por imagem
7.
Cytokine ; 73(1): 79-83, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25743241

RESUMO

BACKGROUND: Chronic Chagas Disease cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi, the rest of the infected subjects remaining asymptomatic (ASY). The Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis. Local expression of IL-18 in CCC myocardial tissue has recently been described. IL-18 could potentially amplify the process by inducing increased expression of IFN-γ which in turn can increase the production of IL-18, thereby creating a positive feedback mechanism. In order to assess the contribution of the IL-18 to susceptibility to Chronic Chagas Disease, we investigated the association between a single nucleotide polymorphism (SNP) located in the IL-18 gene with the risk of developing Chagas cardiomyopathy. METHODS AND RESULTS: We analyzed the rs2043055 marker in the IL18 gene in a cohort of Chagas disease cardiomyopathy patients (n=849) and asymptomatic subjects (n=202). We found a significant difference in genotype frequencies among moderate and severe CCC patients with ventricular dysfunction. CONCLUSIONS: Our analysis suggests that the IL18 rs2043055 polymorphism- or a SNP in tight linkage disequilibrium with it- may contribute to modulating the Chagas cardiomyopathy outcome.


Assuntos
Cardiomiopatia Chagásica/genética , Predisposição Genética para Doença , Interleucina-18/genética , Polimorfismo de Nucleotídeo Único/genética , Estudos de Casos e Controles , Cardiomiopatia Chagásica/fisiopatologia , Doença Crônica , Estudos de Coortes , Feminino , Estudos de Associação Genética , Humanos , Masculino , Volume Sistólico
8.
Cytokine ; 73: 79-83, 2015. tab
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: ses-31265

RESUMO

Background: Chronic Chagas Disease cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy,affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi, the restof the infected subjects remaining asymptomatic (ASY). The Th1 T cell-rich myocarditis plays a pivotalrole in CCC pathogenesis. Local expression of IL-18 in CCC myocardial tissue has recently been described.IL-18 could potentially amplify the process by inducing increased expression of IFN-c which in turn canincrease the production of IL-18, thereby creating a positive feedback mechanism. In order to assess thecontribution of the IL-18 to susceptibility to Chronic Chagas Disease, we investigated the associationbetween a single nucleotide polymorphism (SNP) located in the IL-18 gene with the risk of developingChagas cardiomyopathy.Methods and results: We analyzed the rs2043055 marker in the IL18 gene in a cohort of Chagas diseasecardiomyopathy patients (n = 849) and asymptomatic subjects (n = 202). We found a significant differencein genotype frequencies among moderate and severe CCC patients with ventricular dysfunction.Conclusions: Our analysis suggests that the IL18 rs2043055 polymorphism- or a SNP in tight linkagedisequilibrium with it- may contribute to modulating the Chagas cardiomyopathy outcome. (AU)


Assuntos
Doença de Chagas , Miocardite , Disfunção Ventricular
9.
Arq. bras. cardiol ; 105(1): 28-36, 2015. tab
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: ses-32565

RESUMO

Background: Chagas disease is a cause of dilated cardiomyopathy, and information about left atrial (LA) function inthis disease still lacks.Objective: To assess the different LA functions (reservoir, conduit and pump functions) and their correlation withthe echocardiographic parameters of left ventricular (LV) systolic and diastolic functions.Methods: 10 control subjects (CG), and patients with Chagas disease as follows: 26 with the indeterminate form (GI);30 with ECG alterations (GII); and 19 with LV dysfunction (GIII). All patients underwent M-mode and two-dimensional echocardiography, pulsed-wave Doppler and tissue Doppler imaging. Results: Reservoir function (Total Emptying Fraction: TEF): (p < 0.0001), lower in GIII as compared to CG (p = 0.003),GI (p < 0.001) and GII (p < 0.001). Conduit function (Passive Emptying Fraction: PEF): (p = 0.004), lower in GIII (GIIIand CG, p = 0.06; GI and GII, p = 0.06; and GII and GIII, p = 0.07). Pump function (Active Emptying Fraction: AEF):(p = 0.0001), lower in GIII as compared to CG (p = 0.05), GI (p < 0.0001) and GII (p = 0.002). There was a negative correlation of E/e’average with the reservoir and pump functions (TEF and AEF), and a positive correlation of e’average with s’wave (both septal and lateral walls) and the reservoir, conduit and pump LA functions. Conclusion: An impairment of LA functions in Chagas cardiomyopathy was observed. (Arq Bras Cardiol. 2015;105(1):28-36). (AU)


Assuntos
Doença de Chagas , Cardiomiopatia Chagásica , Disfunção Ventricular , Ecocardiografia
10.
BMC Infect Dis ; 13: 587, 2013 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-24330528

RESUMO

BACKGROUND: Chagas disease, caused by the protozoan Trypanosoma cruzi is endemic in Latin America. Thirty percent of infected individuals develop chronic Chagas cardiomyopathy (CCC), an inflammatory dilated cardiomyopathy that is, by far, the most important clinical consequence of T. cruzi infection. 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. Migration of Th1-type T cells play a major role in myocardial damage. METHODS: Our genetic analysis focused on CCR5, CCL2 and MAL/TIRAP genes. We used the Tag SNPs based approach, defined to catch all the genetic information from each gene. The study was conducted on a large Brazilian population including 315 CCC cases and 118 ASY subjects. RESULTS: The CCL2rs2530797A/A and TIRAPrs8177376A/A were associated to an increase susceptibility whereas the CCR5rs3176763C/C genotype is associated to protection to CCC. These associations were confirmed when we restricted the analysis to severe CCC, characterized by a left ventricular ejection fraction under 40%. CONCLUSIONS: Our data show that polymorphisms affecting key molecules involved in several immune parameters (innate immunity signal transduction and T cell/monocyte migration) play a role in genetic susceptibility to CCC development. This also points out to the multigenic character of CCC, each polymorphism imparting a small contribution. The identification of genetic markers for CCC will provide information for pathogenesis as well as therapeutic targets.


Assuntos
Cardiomiopatia Chagásica/genética , Quimiocina CCL2/genética , Predisposição Genética para Doença , Imunidade Inata , Glicoproteínas de Membrana/genética , Receptores CCR5/genética , Receptores de Interleucina-1/genética , Trypanosoma cruzi/fisiologia , Adulto , Idoso , Brasil , Cardiomiopatia Chagásica/imunologia , Cardiomiopatia Chagásica/parasitologia , Cardiomiopatia Chagásica/prevenção & controle , Quimiocina CCL2/imunologia , Feminino , Genótipo , Humanos , Masculino , Glicoproteínas de Membrana/imunologia , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptores CCR5/imunologia , Receptores de Interleucina-1/imunologia
11.
PLoS One ; 8(12): e83446, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24367596

RESUMO

AIMS: 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.


Assuntos
Actinas/genética , Cardiomiopatia Chagásica/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Actinas/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Miocárdio/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
12.
PLoS Negl Trop Dis ; 6(10): e1867, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23150742

RESUMO

BACKGROUND: Chronic Chagas cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi. Even though the Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis, little is known about the factors controlling inflammatory cell migration to CCC myocardium. METHODS AND RESULTS: Using confocal immunofluorescence and quantitative PCR, we studied cell surface staining and gene expression of the CXCR3, CCR4, CCR5, CCR7, CCR8 receptors and their chemokine ligands in myocardial samples from end-stage CCC patients. CCR5+, CXCR3+, CCR4+, CCL5+ and CXCL9+ mononuclear cells were observed in CCC myocardium. mRNA expression of the chemokines CCL5, CXCL9, CXCL10, CCL17, CCL19 and their receptors was upregulated in CCC myocardium. CXCL9 mRNA expression directly correlated with the intensity of myocarditis, as well as with mRNA expression of CXCR3, CCR4, CCR5, CCR7, CCR8 and their ligands. We also analyzed single-nucleotide polymorphisms for genes encoding the most highly expressed chemokines and receptors in a cohort of Chagas disease patients. CCC patients with ventricular dysfunction displayed reduced genotypic frequencies of CXCL9 rs10336 CC, CXCL10 rs3921 GG, and increased CCR5 rs1799988CC as compared to those without dysfunction. Significantly, myocardial samples from CCC patients carrying the CXCL9/CXCL10 genotypes associated to a lower risk displayed a 2-6 fold reduction in mRNA expression of CXCL9, CXCL10, and other chemokines and receptors, along with reduced intensity of myocarditis, as compared to those with other CXCL9/CXCL10 genotypes. CONCLUSIONS: Results may indicate that genotypes associated to reduced risk in closely linked CXCL9 and CXCL10 genes may modulate local expression of the chemokines themselves, and simultaneously affect myocardial expression of other key chemokines as well as intensity of myocarditis. Taken together our results may suggest that CXCL9 and CXCL10 are master regulators of myocardial inflammatory cell migration, perhaps affecting clinical progression to the life-threatening form of CCC.


Assuntos
Cardiomiopatia Chagásica/genética , Cardiomiopatia Chagásica/patologia , Quimiocina CXCL10/biossíntese , Quimiocina CXCL9/biossíntese , Polimorfismo Genético , Trypanosoma cruzi/patogenicidade , Adolescente , Adulto , Quimiocina CXCL10/genética , Quimiocina CXCL9/genética , Resistência à Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
J Card Fail ; 18(7): 564-8, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22748490

RESUMO

BACKGROUND: Clinical multistage risk assessment associated with electrocardiogram (ECG) and NT-proBNP may be a feasible strategy to screen hypertrophic cardiomyopathy (HCM). We investigated the effectiveness of a screening based on ECG and NT-proBNP in first-degree relatives of patients with HCM. METHODS AND RESULTS: A total of 106 first-degree relatives were included. All individuals were evaluated by echocardiography, ECG, NT-proBNP, and molecular screening (available for 65 individuals). From the 106 individuals, 36 (34%) had diagnosis confirmed by echocardiography. Using echocardiography as the gold standard, ECG criteria had a sensitivity of 0.71, 0.42, and 0.52 for the Romhilt-Estes, Sokolow-Lyon, and Cornell criteria, respectively. Mean values of NT-ProBNP were higher in affected as compared with nonaffected relatives (26.1 vs. 1290.5, P < .001). The AUC of NT-proBNP was 0.98. Using a cutoff value of 70 pg/mL, we observed a sensitivity of 0.92 and specificity of 0.96. Using molecular genetics as the gold standard, ECG criteria had a sensitivity of 0.67, 0.37, and 0.42 for the Romhilt-Estes, Sokolow-Lyon, and Cornell criteria, respectively. Using a cutoff value of 70 pg/mL, we observed a sensitivity of 0.83 and specificity of 0.98. CONCLUSION: Values of NT-proBNP above 70 pg/mL can be used to effectively select high-risk first-degree relatives for HCM screening.


Assuntos
Cardiomiopatia Hipertrófica Familiar/sangue , Cardiomiopatia Hipertrófica Familiar/diagnóstico , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Adulto , Ecocardiografia , Eletrocardiografia , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Curva ROC , Sensibilidade e Especificidade
14.
J Parasitol Res ; 2012: 635873, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22523642

RESUMO

The tandemly repetitive Trypanosoma cruzi B13 protein is an immunodominant antigen among Chagas disease patients. Such repetitive domains may behave as T-independent antigens. However, T cells can recognize B13 epitopes in an HLA class II-restricted fashion and could potentially provide cognate T cell help and boost antibody titers. We assessed whether the presence of HLA class II molecules able to present B13 epitopes to T cells could affect anti-B13 IgG levels in a cognate fashion, in both major clinical forms of chronic Chagas disease. We found no difference between anti-B13 IgG antibody levels between patients carrying HLA class II molecules associated to T cell responses or other alleles. The predominant anti-B13 IgG subclass was IgG1, with negligible IgG2, suggesting a T-dependent, noncognate help for antibody production. In addition, the finding of increased anti-B13 IgG levels in sera from CCC patients indicates that clinical presentation is associated with increased anti-B13 antibody levels.

15.
In. Ianni, Barbara Maria; Mady, Charles. A cardiopatia da Doença de Chagas. São Paulo, Roca, 2009. p.178-188.
Monografia em Português | LILACS | ID: lil-534835
16.
Arq Bras Cardiol ; 91(1): 46-54, 2008 Jul.
Artigo em Inglês, Português | MEDLINE | ID: mdl-18660945

RESUMO

BACKGROUND: NT pro-BNP is a marker of systolic and diastolic dysfunction. OBJECTIVE: To determine NT pro-BNP levels in patients with chagasic, hypertrophic, and restrictive heart diseases, as well as with pericardial diseases, and their relation to echocardiographic measurements of systolic and diastolic dysfunction. METHODS: A total of 145 patients were divided into the following groups: 1) Chagas' heart disease (CHD)--14 patients; 2) hypertrophic cardiomyopathy (HCM)--71 patients; 3) endomyocardial fibrosis (EMF)--26 patients; 4) pericardial effusion (PE)--18 patients; and 5) constrictive pericarditis (CP)--16 patients. The control group was comprised of 40 individuals with no heart disease. The degree of myocardial impairment and pericardial effusion were assessed by two-dimensional echocardiography and the degree of restriction by pulsed Doppler transmitral flow. The diagnosis of CP was confirmed through magnetic resonance imaging. NT pro-BNP levels were determined through electrochemiluminescence immunoassay. RESULTS: NT pro-BNP was increased (p < 0.001) in CHD (median = 513.8 pg/ml), HCM (median = 848 pg/ml), EMF (median = 633 pg/ml), CP (median = 568 pg/ml), and PE (median = 124 pg/ml), when compared with the control group (median = 28 pg/ml). No statistically significant differences were found between CP and EMF (p = 0.14). In the hypertrophic group, NT pro-BNP was correlated with left atrial size (r = 0.40; p < 0.001) and with E/Ea ratio (p < 0.01). In the restrictive group, there was a trend of correlation with E-wave peak velocity (r = 0.439; p = 0.06). CONCLUSION: NT pro-BNP is increased in the different cardiomyopathies and pericardial diseases and is correlated with the degree of systolic and diastolic dysfunction.


Assuntos
Cardiomiopatias/diagnóstico , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Pericardite Constritiva/diagnóstico , Disfunção Ventricular/diagnóstico , Adulto , Biomarcadores/sangue , Cardiomiopatias/sangue , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/fisiopatologia , Cardiomiopatia Restritiva/diagnóstico , Cardiomiopatia Restritiva/fisiopatologia , Estudos de Casos e Controles , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/fisiopatologia , Diástole/fisiologia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/fisiologia , Fragmentos de Peptídeos/fisiologia , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/fisiopatologia , Pericardite Constritiva/sangue , Pericárdio/diagnóstico por imagem , Estudos Prospectivos , Sístole , Ultrassonografia , Disfunção Ventricular/fisiopatologia
17.
Arq. bras. cardiol ; 91(1): 49-54, jul. 2008. graf, tab
Artigo em Inglês, Português | LILACS | ID: lil-486809

RESUMO

FUNDAMENTO: O NT pro-BNP é marcador de disfunção sistólica e diastólica. OBJETIVO: Determinar os níveis de NT pro-BNP em pacientes com cardiopatia chagásica, hipertrófica, restritiva e afecções pericárdicas, e sua relação com medidas ecocardiográficas de disfunção sistólica e diastólica. MÉTODOS: Cento e quarenta e cinco pacientes foram divididos nos respectivos grupos: 1) cardiopatia chagásica (CCh) - 14 pacientes; 2) miocardiopatia hipertrófica (CMH) - 71 pacientes; 3) endomiocardiofibrose (EMF) - 26 pacientes; 4) derrame pericárdico (DP) - 18 pacientes; 5) e pericardite constritiva (PC) - 16 pacientes. Foi constituído um grupo-controle de 40 indivíduos sem doença cardíaca. O grau de acometimento miocárdico e o derrame pericárdico foram avaliados pelo ecocardiograma bidimensional e a restrição pelo Doppler pulsátil do fluxo mitral. O diagnóstico de PC foi confirmado por meio da ressonância magnética. Os níveis de NT pro-BNP foram medidos por imunoensaio com detecção por eletroquimioluminescência. RESULTADOS: O NT pro-BNP esteve aumentado (p < 0,001) na CCh (mediana 513,8 pg/ml), CMH (mediana 848 pg/ml), EMF (mediana 633 pg/ml), PC (mediana 568 pg/ml), DP (mediana 124 pg/ml), quando comparados ao grupo-controle (mediana 28 pg/ml). Não foram observadas diferenças estatisticamente significativas entre PC e EMF (p = 0,14). No grupo hipertrófico, o NT pro-BNP correlacionou-se com tamanho de átrio esquerdo (r = 0,40; p < 0,001) e relação E/Ea (p < 0,01). No grupo restritivo, houve uma tendência de correlação com pico de velocidade de onda E (r = 0,439; p = 0,06). CONCLUSÃO: O NT pro-BNP encontra-se aumentado nas diversas miocardiopatias e afecções pericárdicas, e apresenta relação com o grau de disfunção sistólica e diastólica.


BACKGROUND: NT pro-BNP is a marker of systolic and diastolic dysfunction. OBJECTIVE: To determine NT pro-BNP levels in patients with chagasic, hypertrophic, and restrictive heart diseases, as well as with pericardial diseases, and their relation to echocardiographic measurements of systolic and diastolic dysfunction. METHODS: A total of 145 patients were divided into the following groups: 1) Chagas' heart disease (CHD) - 14 patients; 2) hypertrophic cardiomyopathy (HCM) - 71 patients; 3) endomyocardial fibrosis (EMF) - 26 patients; 4) pericardial effusion (PE) - 18 patients; and 5) constrictive pericarditis (CP) - 16 patients. The control group was comprised of 40 individuals with no heart disease. The degree of myocardial impairment and pericardial effusion were assessed by two-dimensional echocardiography and the degree of restriction by pulsed Doppler transmitral flow. The diagnosis of CP was confirmed through magnetic resonance imaging. NT pro-BNP levels were determined through electrochemiluminescence immunoassay. RESULTS: NT pro-BNP was increased (p < 0.001) in CHD (median = 513.8 pg/ml), HCM (median = 848 pg/ml), EMF (median = 633 pg/ml), CP (median = 568 pg/ml), and PE (median = 124 pg/ml), when compared with the control group (median = 28 pg/ml). No statistically significant differences were found between CP and EMF (p = 0.14). In the hypertrophic group, NT pro-BNP was correlated with left atrial size (r = 0.40; p < 0.001) and with E/Ea ratio (p < 0.01). In the restrictive group, there was a trend of correlation with E-wave peak velocity (r = 0.439; p = 0.06). CONCLUSION: NT pro-BNP is increased in the different cardiomyopathies and pericardial diseases and is correlated with the degree of systolic and diastolic dysfunction.


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cardiomiopatias/diagnóstico , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Pericardite Constritiva/diagnóstico , Disfunção Ventricular/diagnóstico , Biomarcadores/sangue , Estudos de Casos e Controles , Cardiomiopatias/sangue , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/fisiopatologia , Cardiomiopatia Restritiva/diagnóstico , Cardiomiopatia Restritiva/fisiopatologia , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/fisiopatologia , Diástole/fisiologia , Imagem por Ressonância Magnética , Peptídeo Natriurético Encefálico/fisiologia , Estudos Prospectivos , Fragmentos de Peptídeos/fisiologia , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/fisiopatologia , Pericardite Constritiva/sangue , Pericárdio , Sístole , Disfunção Ventricular/fisiopatologia
18.
In. Krieger, José Eduardo. Bases moleculares das Doenças Cardiovasculares: a integração entre a pesquisa e a prática clínica. São Paulo, Atheneu, 2008. p.297-307.
Monografia em Português | LILACS | ID: lil-511096
19.
Arq Bras Cardiol ; 88(5): 552-8, 2007 May.
Artigo em Inglês, Português | MEDLINE | ID: mdl-17589630

RESUMO

BACKGROUND: Patients with sickle cell anemia (SCA) frequently present with episodes of chest pain, alterations in the resting electrocardiogram, and changes in cardiac structure and functions. OBJECTIVE: To evaluate the effect of recurrent episodes of vaso-occlusion on the coronary microcirculation. METHODS: Coronary flow velocity and coronary flow reserve (CFR) of stable patients with SCA (n=10, 5 females, 24.4+/-5.4 years) were measured in the anterior descending coronary artery with transesophageal echocardiogram at baseline and after intravenous adenosine-induced maximum hyperemia, and compared to those of patients with sickle cell trait (TRA, n=10, 5 females, 27.7+/-3.2 years), iron deficiency anemia (IRO, n=8, 8 females, 26.6+/-5.2 years) and control group (NOR, n=10, 5 females, 26.3+/-6.3 years). RESULTS: The SCA group presented increased diastolic coronary flow velocities (p<0.01) at baseline and during maximum hyperemia (67.3+/-14.0 and 198.2+/-37.9 cm/s, respectively) when compared with the other three groups - TRA (34.4+/-11.9 and 114.7+/-36.4 cm/s), IRO (42.4+/-10.4 and 141.0+/-18.7 cm/s) and NOR (38.1+/-10.0 and 126.8+/-24.6 cm/s). However, CFR was normal in the SCA group (3.0+/-0.7) and comparable (p=0.70) to the other groups - TRA (3.4+/-0.8), IRO (3.5+/-1.2), and NOR (3.4+/-0.8). CONCLUSION: Despite the higher coronary flow velocities already observed at baseline and also during maximum hyperemia, CFR is normal in SCA, which suggests preserved coronary microcirculation. The episodes of vaso-occlusion are not responsible for the cardiologic findings in this disease.


Assuntos
Anemia Falciforme/fisiopatologia , Velocidade do Fluxo Sanguíneo/fisiologia , Circulação Coronária/fisiologia , Microcirculação/fisiopatologia , Adulto , Anemia Falciforme/diagnóstico por imagem , Estudos de Casos e Controles , Ecocardiografia Doppler em Cores , Ecocardiografia Transesofagiana , Feminino , Humanos , Masculino , Microcirculação/diagnóstico por imagem , Estudos Prospectivos
20.
Arq. bras. cardiol ; 88(5): 552-558, maio 2007. tab
Artigo em Português | LILACS | ID: lil-453046

RESUMO

FUNDAMENTO: Pacientes com anemia falciforme (FAL) apresentam freqüentemente episódios de dor precordial, possuem alterações eletrocardiográficas em repouso e exibem alterações da estrutura e das funções cardíacas. OBJETIVO: Avaliar o efeito dos episódios repetitivos de vaso-oclusão sobre a microcirculação coronariana. MÉTODOS: Pacientes estáveis com FAL (n = 10, cinco mulheres, 24,4 + 5,4 anos) foram submetidos a medida das velocidades de fluxo coronariano e da reserva de fluxo coronariano (RFC) na artéria coronária descendente anterior por meio de ecocardiografia transesofágica em estado basal e após hiperemia máxima, obtida com adenosina intravenosa. Esses pacientes foram comparados a pacientes com traço falciforme (TRA, n = 10, cinco mulheres, 27,7 + 3,2 anos), anemia ferropriva (FER, n = 8, oito mulheres, 26,6 + 5,2 anos) e grupo controle (NOR, n = 10, cinco mulheres, 26,3 + 6,3 anos). RESULTADOS: O grupo FAL apresentou aumento das velocidades de fluxo coronariano diastólico (p < 0,01) em estado basal e durante hiperemia máxima (67,3 + 14,0 cm/s e 198,2 + 37,9 cm/s, respectivamente), quando comparado aos três outros grupos (TRA, 34,4 + 11,9 cm/s e 114,7 + 36,4 cm/s; FER, 42,4 + 10,4 cm/s e 141,0 + 18,7 cm/s e NOR, 38,1 + 10,0 cm/s e 126,8 + 24,6 cm/s). Entretanto, a RFC foi normal no grupo FAL (3,0 + 0,7) e comparável (p = 0,70) aos demais grupos (TRA, 3,4 + 0,8; FER, 3,5 + 1,2 e NOR, 3,4 + 0,8). CONCLUSÃO: Apesar de maiores velocidades de fluxo coronariano já em estado basal e também durante hiperemia máxima, a RFC é normal na FAL, o que sugere integridade da microcirculação coronariana. Os episódios de vaso-oclusão não são responsáveis pelos achados cardiológicos da doença.


BACKGROUND: Patients with sickle cell anemia (SCA) frequently present with episodes of chest pain, alterations in the resting electrocardiogram, and changes in cardiac structure and functions. OBJECTIVE: To evaluate the effect of recurrent episodes of vaso-occlusion on the coronary microcirculation. METHODS: Coronary flow velocity and coronary flow reserve (CFR) of stable patients with SCA (n=10, 5 females, 24.4±5.4 years) were measured in the anterior descending coronary artery with transesophageal echocardiogram at baseline and after intravenous adenosine-induced maximum hyperemia, and compared to those of patients with sickle cell trait (TRA, n=10, 5 females, 27.7±3.2 years), iron deficiency anemia (IRO, n=8, 8 females, 26.6±5.2 years) and control group (NOR, n=10, 5 females, 26.3±6.3 years). RESULTS: The SCA group presented increased diastolic coronary flow velocities (p<0.01) at baseline and during maximum hyperemia (67.3±14.0 and 198.2±37.9 cm/s, respectively) when compared with the other three groups - TRA (34.4±11.9 and 114.7±36.4 cm/s), IRO (42.4±10.4 and 141.0±18.7 cm/s) and NOR (38.1±10.0 and 126.8±24.6 cm/s). However, CFR was normal in the SCA group (3.0±0.7) and comparable (p=0.70) to the other groups - TRA (3.4±0.8), IRO (3.5±1.2), and NOR (3.4±0.8). CONCLUSION: Despite the higher coronary flow velocities already observed at baseline and also during maximum hyperemia, CFR is normal in SCA, which suggests preserved coronary microcirculation. The episodes of vaso-occlusion are not responsible for the cardiologic findings in this disease.


Assuntos
Adulto , Feminino , Humanos , Masculino , Anemia Falciforme/fisiopatologia , Velocidade do Fluxo Sanguíneo/fisiologia , Circulação Coronária/fisiologia , Microcirculação/fisiopatologia , Anemia Falciforme , Estudos de Casos e Controles , Ecocardiografia Doppler em Cores , Ecocardiografia Transesofagiana , Microcirculação , Estudos Prospectivos
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