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1.
Vet J ; 244: 16-22, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30825889

RESUMO

The study objective was to investigate heart-fatty acid binding protein (HFABP) concentrations in dogs with degenerative valvular disease (MVD) and dilated cardiomyopathy (DCM), and its potential as a prognostic factor. Plasma HFABP, N-terminal pro brain natriuretic peptide (NTproBNP) and serum cardiac troponin I (cTnI) levels were measured in 21 control dogs, 23 dogs with MVD and 13 dogs with DCM, with repeated sampling at 1 and 3 months after initial presentation. All dogs were followed up after 6 and 12 months to verify survival. Heart-fatty acid binding protein concentrations were significantly higher in dogs with MVD and DCM than controls at initial presentation, and after 1 month in dogs with MVD. For dogs with DCM, a significant reduction in HFABP levels over time was observed. Comparing ACVIM stages, highest HFABP concentrations were detected in ACVIM stage C dogs compared to stage B, with the lowest levels seen in controls, and a reduction over time in stage C dogs was present. Similarly, cTnI concentrations were higher in DCM and stage C in comparison to control dogs and reduced over time, while NTproBNP concentrations were only higher in diseased dogs at 1 month. Heart-fatty acid binding protein and cTnI levels at initial presentation and ACVIM disease stage were independent predictors of survival in a univariate analysis. The elevation of HFABP in dogs with MVD and DCM in comparison to controls, its association with disease severity, and its potential in predicting reduced survival, suggest that HFABP might be useful as marker for canine MVD and DCM.


Assuntos
Biomarcadores/metabolismo , Cardiomiopatia Dilatada/veterinária , Doenças do Cão/metabolismo , Proteína 3 Ligante de Ácido Graxo/metabolismo , Doenças das Valvas Cardíacas/veterinária , Animais , Biomarcadores/sangue , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/metabolismo , Estudos de Casos e Controles , Doenças do Cão/sangue , Cães , Proteína 3 Ligante de Ácido Graxo/sangue , Feminino , Doenças das Valvas Cardíacas/sangue , Doenças das Valvas Cardíacas/metabolismo , Masculino , Peptídeo Natriurético Encefálico/sangue , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/metabolismo , Valor Preditivo dos Testes , Troponina I/sangue , Troponina I/metabolismo
2.
J Pineal Res ; 66(4): e12564, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30715754

RESUMO

BACKGROUND: Melatonin is a multifunctional indolamine and has a cardioprotective role in a variety of cardiovascular processes via antioxidant, anti-inflammatory, antihypertensive, antithrombotic, and antilipemic effects. It has been reported that lower levels of circulating melatonin are significantly associated with a higher risk of acute myocardial infarction (AMI) and later cardiac remodeling. However, levels of melatonin in patients with dilated cardiomyopathy (DCM) and associations between melatonin levels and cardiac function remain unclear. METHODS AND RESULTS: We measured and compared plasma levels of melatonin in 61 control subjects, 81 AMI patients, and 77 DCM patients. Plasma levels of melatonin were progressively decreased from 71.9 pg/mL in the control group to 52.6 pg/mL in the DCM group and 21.9 pg/mL in the AMI group. Next, we examined associations of melatonin levels with parameters of laboratory data, echocardiography, and right-heart catheterization. In the DCM patients, circulating melatonin showed significant correlations with both high-sensitivity troponin T (R = -0.422, P < 0.001) and cardiac output (R = 0.431, P = 0.003), but not with B-type natriuretic peptide (BNP), left ventricular ejection fraction (LVEF), pulmonary artery wedge pressure, or pulmonary artery pressure. CONCLUSION: Patients with not only AMI but also DCM had lower circulating melatonin levels. Circulating melatonin levels appear to correlate with myocardial injury and cardiac output in DCM patients.


Assuntos
Cardiomiopatia Dilatada/sangue , Melatonina/sangue , Doença Aguda , Idoso , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Peptídeo Natriurético Encefálico/sangue , Troponina/sangue
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.
J Vet Intern Med ; 33(1): 54-63, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30536428

RESUMO

BACKGROUND: Echocardiography and 24-hour ECG are the gold standard tests to diagnose dilated cardiomyopathy (DCM) in Doberman Pinschers (DP), but myocardial damage might be detected earlier using a high-sensitivity cardiac troponin I (hs-cTnI) assay. OBJECTIVE: To evaluate and compare an hs-cTnI assay (Advia Centaur TnI-Ultra assay) with a conventional cTnI assay in DP with different stages of DCM and in healthy DP. ANIMALS: Three hundred forty-five examinations from 162 DP with and 179 DP without DCM. METHODS: Prospective longitudinal study. Dogs were allocated into 6 groups based on echocardiographic and 24-hour ECG criteria: (1) healthy group (179 dogs), (2) last-normal group (29 dogs), which included dogs that were considered to be healthy at the time of their examination but were assigned to the last-normal group retrospectively when DCM was diagnosed at their next examination within 1.5 years, (3) only arrhythmias (45 dogs, 119 examinations), (4) only echocardiographic changes (24 dogs, 61 examinations), (5) echocardiographic changes with ventricular premature complexes (41 dogs, 100 examinations), and (6) decompensated (23 dogs, 36 examinations). Hs-cTnI and conventional cTnI concentration measurements were performed and compared. RESULTS: A cutoff value of hs-cTnI concentration >0.113 ng/mL had a sensitivity of 81.2% and a specificity of 73.2% to identify the presence of DCM. The conventional cTnI assay showed a similar test performance, but the hs-cTnI assay identified more dogs (21/29 dogs, 72%) in the last-normal group compared to the conventional cTnI test (18/29 dogs, 62%). CONCLUSIONS AND CLINICAL IMPORTANCE: The hs-cTnI is an additional test with good potential to identify early DCM.


Assuntos
Cardiomiopatia Dilatada/veterinária , Doenças do Cão/sangue , Animais , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/diagnóstico , Estudos de Casos e Controles , Doenças do Cão/diagnóstico , Cães/sangue , Ecocardiografia/veterinária , Eletrocardiografia/veterinária , Feminino , Estudos Longitudinais , Masculino , Estudos Prospectivos , Troponina I
5.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 43(1): 35-40, 2018 Jan 28.
Artigo em Chinês | MEDLINE | ID: mdl-30154289

RESUMO

OBJECTIVE: To examine the role of LY294002 in cardiac function and myocardial structure in dilated cardiomyopathy (DCM) rats.
 Methods: Fifty-two male SD rats were randomly assigned to a control group (n=16) and a DCM group (n=36). The DCM rats were induced by intraperitoneal injection of adriamycin, and the control rats were given normal saline. After observation for 2 weeks, 6 rats from each group were killed randomly. In the end of the 8th week, the 24 DCM rats were randomly assigned to a DCM group (n=12) and a LY294002 group (n=12), which were given normal saline and LY294002, respectively. In the end of the 8th week and 16th week, the cardiac function was analyzed by ultrasonic cardiogram (UCG) and the plasma was collected to test the level of N-terminal pro-brain natriuretic peptide (NT-pro BNP). HE and Van Gieson (VG) staining were performed to calculate the collagen volume fraction (CVF).
 Results: Compared with the control group, the left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD) and NT-proBNP level of in the DCM rats were increased obviously, while the left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS) in the DCM rats were decreased obviously (P<0.01). These changes were consistent with DCM characteristics. Compared with the DCM group, the LVEDD, LVESD and NT-proBNP levels in the LY294002 group were decreased, while the LVEF and LVFS were increased (P<0.05). Histopathology showed that the myocardium in the DCM rats was fibrotic and the CVF was increased compared with the control rats (P<0.01). The myocardial structure was improved in the LY294002 group compared to the DCM group.
 Conclusion: LY294002 can reduce the myocardial fibrosis in the DCM rats and improve the cardiac function.


Assuntos
Cardiomiopatia Dilatada/tratamento farmacológico , Cardiomiopatia Dilatada/fisiopatologia , Miocárdio/patologia , Animais , Fator Natriurético Atrial/sangue , Cardiomiopatias , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/patologia , Colágeno/análise , Fibrose , Coração/efeitos dos fármacos , Masculino , Precursores de Proteínas/sangue , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Função Ventricular Esquerda/fisiologia
6.
Dis Markers ; 2018: 2958219, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30018673

RESUMO

Objectives: Studies have evaluated the association of galectin-3 and outcome in patients with heart failure. However, there is still scarce evidence concerning the clinical usefulness and predictive value of galectin-3 for left ventricular reverse remodeling (LVRR) in patients with recent-onset dilated cardiomyopathy (RODCM). Patients and Methods: Baseline galectin-3 was measured in 57 patients with RODCM. All patients were followed for at least 12 months. The study end point was LVRR at 12 months, defined as an absolute improvement of the left ventricular ejection fraction of ≥10% to a final value of ≥35%, accompanied by a decrease in the left ventricular end diastolic diameter of at least 10%, as assessed by echocardiography. In receiver operating characteristic curve analysis, the optimum cut-off value for baseline galectin-3 with the highest Youden index was 59 ng/ml. Results: Overall, LVRR at 12 months was observed in 38 patients (66%). In a univariate analysis, NYHA functional class and baseline galectin-3 levels were associated with LVRR. After adjustment for covariates, galectin-3 remained an independent predictor for LVRR. Conclusions: Our study suggests that baseline galectin-3 is an independent predictor of LVRR. Low levels of galectin-3 may be regarded a useful biomarker of favorable ventricular remodeling in patients with RODCM.


Assuntos
Cardiomiopatia Dilatada/sangue , Galectina 3/sangue , Remodelação Ventricular , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Cardiomiopatia Dilatada/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
7.
Cell Physiol Biochem ; 46(5): 1939-1950, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29719295

RESUMO

BACKGROUND/AIMS: MicroRNAs (miRNAs) can be used as biomarkers for cardiovascular diseases, especially for heart failure. However, there are few reports on serum exosomal miRNA biomarkers in patients with acute heart failure (AHF) due to Dilated cardiomyopathy (DCM). METHODS: We analyzed 3 different serum exosomal miRNAs (exo-miR-92b-5p, exo-miR-192-5p, and exo-miR-320a) in 43 patients with DCM-AHF and 34 healthy volunteers as a control group (CG) by using exosome separation followed by a quantitative reverse-transcript PCR assay. Exosomes were identified by electron microscopy, NaNOZS-90, and western blot analyses (CD63 and Hsp70). RESULTS: Serum exo-miR-92b-5p expression was increased in DCM-AHF patients compared to the CG (Mann-Whitney U-test: P < 0.001). Exo-miR-92b-5p was positively related to age and some ultrasound data (Spearman's correlation: exo-miR-92b-5p vs. age, r = 0.297, P = 0.014; exo-miR-92b-5p vs. left atrial diameter, r = 0.431, P < 0.001; exo-miR-92b-5p vs. left ventricular diastolic diameter, r = 0.419, P < 0.001; exo-miR-92b-5p vs. left ventricular systolic diameter, r = 0.446, P < 0.001). Exo-miR-92b-5p was also negatively related to other ultrasound data (Spearman's correlation: exo-miR-92b-5p vs. left ventricular fraction shortening, r = -0.497, P < 0.001; exo-miR-92b-5p vs. left ventricular ejection fraction, r = -0.482, P < 0.001). The discrimination of DCM-AHF patients from the CG by exo-miR-92b-5p was demonstrated by a receiver operating characteristic curve (exo-miR-92b-5p: cutoff value = 0.0023, area under the curve = 0.808, P < 0.001, sensitivity = 62.8%, specificity = 85.3%). CONCLUSION: Serum exo-miR-92b-5p is a potential biomarker for the diagnosis of DCM-AHF.


Assuntos
Cardiomiopatia Dilatada/sangue , Insuficiência Cardíaca/sangue , MicroRNAs/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Cardiomiopatia Dilatada/complicações , Cardiomiopatia Dilatada/genética , Exossomos/genética , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/genética , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Adulto Jovem
8.
Biomed Res Int ; 2018: 2739014, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29682528

RESUMO

Zinc is essential for the maintenance of normal cellular structure and functions. Zinc dyshomeostasis can lead to many diseases, such as cardiovascular disease. However, there are conflicting reports on the relationship between serum zinc levels and heart failure (HF). The purpose of the present study is to explore the relationship between serum zinc levels and HF by using a meta-analysis approach. PubMed, Web of Science, and OVID databases were searched for reports on the association between serum zinc levels and HF until June 2016. 12 reports with 1453 subjects from 27 case-control studies were chosen for the meta-analysis. Overall, the pooled analysis indicated that patients with HF had lower zinc levels than the control subjects. Further subgroup analysis stratified by different geographic locations also showed that HF patients had lower zinc levels than the control subjects. In addition, subgroup analysis stratified by HF subgroups found that patients with idiopathic dilated cardiomyopathy (IDCM) had lower zinc levels than the control subjects, except for patients with ischemic cardiomyopathy (ICM). In conclusion, the results of the meta-analysis indicate that there is a significant association between low serum zinc levels and HF.


Assuntos
Insuficiência Cardíaca/sangue , Zinco/sangue , Animais , Cardiomiopatia Dilatada/sangue , Estudos de Casos e Controles , Humanos , Fatores de Risco
9.
Orv Hetil ; 159(13): 526-530, 2018 Apr.
Artigo em Húngaro | MEDLINE | ID: mdl-29577764

RESUMO

Dilated cardiomyopathy is the main cause of heart transplantation. The etiology is unknown in almost half of the cases. Many cardiac specific antibodies have been identified till now which can cause decreased cardiac function, ventricular tachycardia or sudden heart death. The prognosis of DCM is poor despite the development of medical treatment. Immunoadsorption is hopeful since, with the removal of antibodies, cardiac function and NYHA class can improve and LVAD/heart transplantation-free survival can be prolonged. At the University of Debrecen, Faculty of Medicine, Department of Internal Medicine, Division of Angiology, Intensive Care and Therapeutic Apheresis Unit we performed the first immunoadsorption. Our patient was a 43-year-old man with idiopathic dilated cardiomyopathy, NYHA class IV, a heart transplantation candidate, whose cardiac specific antibody, type IgG was indentified by Western blot. Before the treatment he had ejection fraction of 18%. Discussing with his cardiologists we decided for immunoadsorption therapy. We performed 5 cycles on consecutive days in Intensive Care Unit. After 1 month we detected improvement in exercise capacity. We detected improvement in isovolemic contraction (from 465 mmHg/s to 575 mmHg/s), increased stroke volume (from 49 ml to 66 ml). After 3 months we repeated SPECT investigation which showed improvement in ejection fraction, from 18% to 32%. Orv Hetil. 2018; 159(13): 532-536.


Assuntos
Cardiomiopatia Dilatada/terapia , Técnicas de Imunoadsorção , Adulto , Cardiomiopatia Dilatada/sangue , Humanos , Hungria , Imunoglobulina G/sangue , Masculino , Volume Sistólico , Resultado do Tratamento
10.
Transplant Proc ; 50(2): 650-652, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29579878

RESUMO

BACKGROUND: Patients with dilated cardiomyopathy (DCM) and left ventricular dysfunction have a varied clinical course, not only dependent on left ventricular ejection fraction (LVEF) and symptoms. Finding prognostic markers for stratification in these 2 conditions is a critical area of research. Our aim was determine the prognostic value of blood panel basic parameters. METHODS: We analyzed all patients with idiopathic or familial DCM and LVEF <30% coming to our heart failure unit for evaluation for non-urgent heart transplant during the period of 2009 to 2011. With 5 years of follow-up data, we could study the prognostic value of blood panel parameters. Moreover, we determined the combination of platelet count and neutrophil to lymphocyte ratio score from the BIOSTAT-CHF study. RESULTS: Eighty-seven patients were included in the study. After 5 years follow-up, 49 patients (57%) remain alive (group A) and 38 (43%) either died or needed a heart transplant. There were no differences between groups with regard to age or sex. Patients with good progress showed a lower red cell distribution width (RDW), a higher lymphocyte count, and a lower neutrophil/lymphocyte ratio in the initial blood panel. An RDW ≥15% was associated with long-term mortality or heart transplant. CONCLUSION: A basic blood panel could be a useful tool in assessing patients with heart failure. Larger studies are necessary to confirm our findings. A multimarker strategy could also be useful for stratification of patients with advanced heart failure.


Assuntos
Biomarcadores/sangue , Cardiomiopatia Dilatada/sangue , Insuficiência Cardíaca/sangue , Eritrócitos/patologia , Feminino , Transplante de Coração , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Contagem de Plaquetas , Prognóstico
11.
Biol Trace Elem Res ; 183(1): 40-48, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28819918

RESUMO

Keshan disease (KD) is an endemic cardiomyopathy with high mortality. Selenium (Se) and zinc (Zn) deficiencies are closely related to KD. The molecular mechanism of KD pathogenesis is still unclear. There are only few studies on the interaction of trace elements and proteins associated with the pathogenesis of KD. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-coupled two-dimensional liquid chromatography tandem mass spectrometry (2DLC-MS/MS) technique analysis was used to analyze the differential expression of proteins from serum samples. Comparative Toxicogenomics Database (CTD) was used to screen Se- and Zn-associated proteins. Then, pathway and network analyses of Se- and Zn-associated proteins were constituted by Cytoscape ClueGO and GeneMANIA plugins. One hundred and five differentially expressed proteins were obtained by 2DLC-MS/MS, among them 19 Se- and 3 Zn-associated proteins. Fifty-two pathways were identified from ClueGO and 1 network from GeneMANIA analyses. The results showed that Se-associated proteins STAT3 and MAPK1 and Zn-associated proteins HIF1A and PARP1, the proteins involved in HIF-1 signaling pathway and apoptosis pathway, may play significant roles in the pathogenesis of KD. The approach of this study would be also beneficial for further dissecting molecular mechanism of other trace element-associated disease.


Assuntos
Cardiomiopatias/sangue , Cardiomiopatia Dilatada/sangue , Bases de Dados Factuais , Infecções por Enterovirus/sangue , Regulação da Expressão Gênica , Metaloproteínas/sangue , Selênio/sangue , Zinco/sangue , Idoso , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Proteômica
12.
Adv Med Sci ; 63(1): 160-166, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29120858

RESUMO

INTRODUCTION: Serum markers of fibrosis provide an insight into extracellular matrix (ECM) fibrosis in heart failure (HF) and dilated cardiomyopathy (DCM). However, their role as predictors of cardiovascular (CV) events in DCM is poorly understood. METHODS: This is an observational, prospective cohort study. 70 DCM patients (48±12.1years, ejection fraction - EF 24.4±7.4) were recruited. Markers of collagen type I and III synthesis - procollagen type I and III carboxy- and amino-terminal peptides (PICP, PIIICP, PINP, PIIINP), fibrosis controlling factors - ostepontin (OPN), transforming growth factor (TGF1-ß) and connective tissue growth factor (CTGF), and matrix metalloproteinases (MMP-2, MMP-9) and tissue inhibitor (TIMP-1), were measured in serum. All patients underwent endomyocardial biopsy. The end-point was combined with CV death and urgent HF hospitalization. Patients were divided into two groups: those who did (group 1, n=45) and did not reach (group 2, n=25) an end-point. RESULTS: Over a 12-month period of observation, 6 CV deaths and 19 HF hospitalizations occurred. Qualitative and quantitative measures of ECM fibrosis were similar in both groups. The levels of all of the markers of collagen synthesis, TGF1-ß, MMP-9 and TIMP-1 were similar, however, OPN, CTGF and MMP-2 were significantly lower in group 1. CONCLUSIONS: Invasively-determined fibrosis levels were not related with CV outcomes in DCM. Out of the 11 markers of fibrosis under study, only OPN was found to be related to CV outcomes. OPN is not only the pivotal protein controlling fibrosis, but may also serve as a biomarker associated with prognosis.


Assuntos
Biomarcadores/sangue , Cardiomiopatia Dilatada/sangue , Osteopontina/sangue , Intervalo Livre de Doença , Determinação de Ponto Final , Matriz Extracelular/metabolismo , Feminino , Fibrose , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Resultado do Tratamento
13.
Cell Physiol Biochem ; 43(4): 1515-1525, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29035886

RESUMO

BACKGROUND/AIMS: The imbalance of Treg/Th17 cells plays important role in the pathogenesis of dilated cardiomyopathy (DCM). Response gene to complement (RGC)-32 is a cell cycle regulator that plays an important role in cell proliferation. We evaluated whether the upregulation of RGC-32 was implicated in the homeostasis of Treg/Th17 cells in DCM. METHODS: The levels of plasma RGC-32, IL-17 and TGF-ß1, and the frequencies of circulating CD4+ RGC-32+ T cells, Th17 and Treg cells in patients with DCM were determined by Cytokine-specific sandwich ELISA and the flow cytometer (FCM), respectively. RESULTS: A significant elevation of plasma RGC-32 in patients with DCM compared with healthy control (HC) subjects was observed. This upregulation was associated with an increase in frequency of Th17 and a decrease in frequency of Treg cells. To further assessed the role of RGC-32, we investigated the effects of RGC-32 up- or down-regulation on frequencies of Th17 and Treg cells in peripheral blood mononuclear cells (PBMCs) from subjects. Importantly, overexpression of RGC-32 was accompanied by an augmentation of Th17 and a reduction of Treg expression. CONCLUSION: In summary, our study demonstrated the up-regulation of RGC-32 contributed to the imbalance of Treg/Th17 cells in patients with DCM.


Assuntos
Cardiomiopatia Dilatada/sangue , Proteínas de Ciclo Celular/sangue , Proteínas Musculares/sangue , Proteínas do Tecido Nervoso/sangue , Linfócitos T Reguladores/patologia , Células Th17/patologia , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/patologia , Proteínas de Ciclo Celular/genética , Citocinas/análise , Citocinas/sangue , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Musculares/genética , Proteínas do Tecido Nervoso/genética
14.
Rev Port Cardiol ; 36(10): 709-716, 2017 Oct.
Artigo em Inglês, Português | MEDLINE | ID: mdl-28989069

RESUMO

INTRODUCTION: Biomarkers in dilated cardiomyopathy (DCM) reflect various pathobiological processes, including neurohormonal activation, oxidative stress, matrix remodeling, myocyte injury and myocyte stretch. We assessed the role of biomarkers in clinical and echocardiographic parameters and in left ventricular (LV) reverse remodeling (LVRR). METHODS: In this prospective study of 50 DCM patients (28 men, aged 59±10 years) with LV ejection fraction (LVEF) <40%, LVRR was defined as an increase of >10 U in LVEF after optimal medical therapy. RESULTS: Baseline LVEF was 25.4±9.8% and LV end-diastolic diameter (LVEDD)/body surface area (BSA) was 34.2±4.5 mm/m2. LVRR occurred in 34% of patients within 17.6±15.6 months. No correlation was found between B-type natriuretic peptide (BNP), 25-hydroxyvitamin D (25(OH)D), CA-125, high-sensitivity C-reactive protein (hs-CRP), lipoprotein(a) [Lp(a)], noradrenaline, adrenaline, renin or aldosterone and LVRR. Patients in NYHA class III or IV, with pulmonary congestion or ankle edema, had higher CA-125, cystatin C, BNP and hs-CRP levels (p<0.05). CA-125 was correlated with BNP (r=0.61), hs-CRP (r=0.56) and uric acid (r=0.52) (all p=0.01). BNP correlated directly with LVEDD (r=0.49), LV volumes (r=0.51), pulmonary artery systolic pressure (PASP) (r=0.43) and E/e' (r=0.31), and was inversely correlated with LVEF (r=-0.50) and e' velocity (r=-0.32) (p<0.05). CA-125 was positively correlated with left atrial volume/BSA (r=0.46), E/A ratio (r=0.60) and PASP (r=0.49) (p<0.05). CONCLUSIONS: No correlation was found between biomarkers and LVRR, but CA-125, BNP and hs-CRP were predictors of clinical severity and congestion. BNP correlated with parameters of systolic and diastolic dysfunction, while CA-125 correlated with measures of diastolic dysfunction.


Assuntos
Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/diagnóstico por imagem , Ecocardiografia , Remodelação Ventricular , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença
15.
J Vet Cardiol ; 19(5): 405-415, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28965673

RESUMO

BACKGROUND: Dilated cardiomyopathy (DCM) is the most common cardiac disease in large breed dogs and is inherited in Doberman Pinschers with a high prevalence (58%). OBJECTIVE: The European Society for Veterinary Cardiology convened a task force to formulate screening guidelines for DCM in Dobermans. RECOMMENDATIONS: Screening for occult DCM in Dobermans should start at three years of age and use both Holter monitoring and echocardiography. Yearly screening over the life of the dog is recommended, as a one-time screening is not sufficient to rule out future development of DCM. The preferred echocardiographic method is the measurement of the left ventricular volume by Simpson's method of discs (SMOD). Less than 50 single ventricular premature complexes (VPCs) in 24 h are considered to be normal in Dobermans, although detection of any number of VPCs is cause for concern. Greater than 300 VPCs in 24 h or two subsequent recordings within a year showing between 50 and 300 VPCs in 24 h is considered diagnostic of occult DCM in Dobermans regardless of the concurrent echocardiographic findings. The guidelines also provide recommendations concerning ancillary tests, that are not included in the standard screening protocol, but which may have some utility when recommended tests are not available or financially untenable on an annual basis. These tests include assay of cardiac biomarkers (Troponin I and N-Terminal pro-B-type Natriuretic Peptide) as well as a 5-min resting electrocardiogram (ECG). CONCLUSION: The current guidelines should help to establish an early diagnosis of DCM in Dobermans.


Assuntos
Cardiomiopatia Dilatada/veterinária , Doenças do Cão/diagnóstico , Animais , Biomarcadores/sangue , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/diagnóstico por imagem , Cães , Ecocardiografia/veterinária , Eletrocardiografia/veterinária , Eletrocardiografia Ambulatorial/veterinária , Europa (Continente) , Linhagem , Guias de Prática Clínica como Assunto , Sociedades Médicas , Medicina Veterinária
16.
Am J Cardiol ; 120(11): 2049-2055, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28942941

RESUMO

Iron deficiency (FeD), with or without anemia, in adults with heart failure (HF) is associated with poor outcomes, which can be improved with replacement therapy. A similar therapeutic opportunity may exist for children; however, iron laboratory measurements and FeD have not been described in pediatric patients with HF. A single-center, retrospective study was conducted on 28 patients <21 years old with a diagnosis of dilated cardiomyopathy and HF who had iron laboratories (serum iron, iron saturation, and ferritin) performed. The mean (standard deviation) age at time of laboratory collection was 10.3 (5.5) years. Twenty-seven patients (96.4%) met the criteria for FeD. Serum iron and iron saturation were significantly associated with inpatient hospitalization, being on inotropic medications, or having stage D HF. Low-serum iron was associated with a higher left ventricular end-diastolic dimension and left ventricular end-systolic dimension z-score by echocardiography ((ß -2.58, 95% confidence interval [CI] -4.76, -0.40, p = 0.02) and (ß -2.43, 95% CI -4.70, -0.17, p = 0.04)), respectively. Low ferritin was associated with higher mortality (relative risk 0.29, 95% CI 0.12, 0.70, p = 0.006). In conclusion, FeD was common in this pediatric cohort with more advanced HF. Iron profile abnormalities were associated with worse HF severity and outcomes including mortality.


Assuntos
Anemia Ferropriva/sangue , Cardiomiopatia Dilatada/complicações , Insuficiência Cardíaca/sangue , Ventrículos do Coração/fisiopatologia , Ferro/deficiência , Função Ventricular Esquerda/fisiologia , Anemia Ferropriva/complicações , Biomarcadores/sangue , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/diagnóstico , Criança , Progressão da Doença , Ecocardiografia , Feminino , Ferritinas/sangue , Seguimentos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Ferro/sangue , Masculino , Prognóstico , Estudos Retrospectivos , Volume Sistólico
17.
Ann Biol Clin (Paris) ; 75(5): 557-561, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28958965

RESUMO

A five-year-old boy is presented to Necker hospital for a dilated hypertrophic cardiomyopathy. The implantation of the Berlin Heart Excor® ventricular assist device was performed. This pediatric-sized Berlin Heart® device provides mechanical support for young infants and children of all ages to sustain the failing cardiac circulation over several months, until either recovery of myocardial function or heart transplantation. It remains difficult to identify patients with sufficient recovery and the right time for explantation of the Berlin Heart®. Currently, the decision as to whether a patient should be weaned from the system is mainly based on echocardiographic data. Humoral biomarker, associated to echocardiographic features, would be helpful to identify children who might recover without heart transplantation. We observed that our young patient presented highly elevated BNP plasma levels before mechanical support, and a significant decrease during Berlin Heart® support. Monitoring levels of BNP can be helpful to detect appropriate unloading of the heart as a precondition for recovery. During pump-stop maneuvers, BNP should be regarded in combination with clinical and hemodynamic status of the patients, associated with echocardiographic data.


Assuntos
Cardiomiopatia Dilatada/terapia , Coração Auxiliar , Peptídeo Natriurético Encefálico/sangue , Biomarcadores/sangue , Cardiomiopatia Dilatada/sangue , Pré-Escolar , Humanos , Masculino , Monitorização Fisiológica/métodos
18.
Eur J Hum Genet ; 25(11): 1195-1201, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28853722

RESUMO

Dilated cardiomyopathy (DCM) is extremely heterogeneous with a large proportion due to dominantly inherited disease-causing variants in sarcomeric genes. Recessive metabolic diseases may cause DCM, usually with onset in childhood, and in the context of systemic disease. Whether metabolic defects can also cause adult-onset DCM is currently unknown. Therefore, we performed an extensive metabolic screening in 36 consecutive adult-onset DCM patients. Diagnoses were confirmed by Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). Measurement of propionyl-CoA carboxylase (PCC) activity was done in fibroblasts. Whole exome sequencing (WES) data of 157 additional DCM patients were analyzed for genetic defects. We found a metabolic profile characteristic for propionic acidemia in a patient with severe DCM from 55 years of age. Genetic analysis demonstrated compound heterozygous variants in PCCA. Enzymatic activity of PCC in fibroblasts was markedly reduced. A targeted analysis of the PCCA and PCCB genes using available WES data from 157 further DCM patients subsequently identified another patient with propionic acidemia. This patient had compound heterozygous variants in PCCB, and developed severe DCM from 42 years of age. Adult-onset DCM can be caused by propionic acidemia, an autosomal recessive inheritable metabolic disorder usually presenting as neonatal or childhood disease. Current guidelines advise a low-protein diet to ameliorate or prevent detrimental aspects of the disease. Long-term follow-up of a larger group of patients may show whether this diet would also ameliorate DCM. Our results suggest that diagnostic metabolic screening to identify propionic acidemia and related disorders in DCM patients is justified.


Assuntos
Cardiomiopatia Dilatada/genética , Metilmalonil-CoA Descarboxilase/genética , Acidemia Propiônica/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/etiologia , Cardiomiopatia Dilatada/urina , Células Cultivadas , Feminino , Fibroblastos/metabolismo , Heterozigoto , Humanos , Masculino , Metilmalonil-CoA Descarboxilase/metabolismo , Pessoa de Meia-Idade , Mutação , Linhagem , Acidemia Propiônica/genética
19.
Circulation ; 136(16): 1528-1544, 2017 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-28838933

RESUMO

BACKGROUND: Biochemical DNA modification resembles a crucial regulatory layer among genetic information, environmental factors, and the transcriptome. To identify epigenetic susceptibility regions and novel biomarkers linked to myocardial dysfunction and heart failure, we performed the first multi-omics study in myocardial tissue and blood of patients with dilated cardiomyopathy and controls. METHODS: Infinium human methylation 450 was used for high-density epigenome-wide mapping of DNA methylation in left-ventricular biopsies and whole peripheral blood of living probands. RNA deep sequencing was performed on the same samples in parallel. Whole-genome sequencing of all patients allowed exclusion of promiscuous genotype-induced methylation calls. RESULTS: In the screening stage, we detected 59 epigenetic loci that are significantly associated with dilated cardiomyopathy (false discovery corrected P≤0.05), with 3 of them reaching epigenome-wide significance at P≤5×10-8. Twenty-seven (46%) of these loci could be replicated in independent cohorts, underlining the role of epigenetic regulation of key cardiac transcription regulators. Using a staged multi-omics study design, we link a subset of 517 epigenetic loci with dilated cardiomyopathy and cardiac gene expression. Furthermore, we identified distinct epigenetic methylation patterns that are conserved across tissues, rendering these CpGs novel epigenetic biomarkers for heart failure. CONCLUSIONS: The present study provides to our knowledge the first epigenome-wide association study in living patients with heart failure using a multi-omics approach.


Assuntos
Cardiomiopatia Dilatada/genética , Metilação de DNA , Epigênese Genética , Epigenômica/métodos , Loci Gênicos , Insuficiência Cardíaca/genética , Ventrículos do Coração/química , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/diagnóstico , Estudos de Casos e Controles , Ilhas de CpG , Perfilação da Expressão Gênica , Marcadores Genéticos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Fenótipo , RNA Mensageiro/genética , Análise de Sequência de RNA
20.
Heart Lung ; 46(5): 369-374, 2017 Sep - Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28779903

RESUMO

BACKGROUND: Peri-partum cardiomyopathy (PPCM) is a clinical heart failure that usually develops during the final stage of pregnancy or the first months following delivery. High maternal serum uric acid concentrations have been previous associated with heart failure and preeclampsia. OBJECTIVES: 1) To explored the clinical characteristics of PPCM patients; and 2) to determine the association between maternal serum uric acid concentrations and PPCM. METHODS: This is a retrospective population based case control study. Cases and controls were matched 1:4 (for gestational age, medical history of cardiac conditions and creatinine); conditional logistic regression was used to identify clinical parameters that were associated with PPCM. RESULTS: The prevalence of peripartum cardiomyopathy at our institution was 1-3832 deliveries (42/160,964). In a matched multivariate analysis high maternal serum uric acid concentrations were associated with PPCM (O.R 1.336, 95% C.I 1.003-1.778). Uric acid concentrations were higher within the Non-Jewish patients and mothers of male infant with PPCM in compare to those without PPCM (p value 0.003 and 0.01 respectively). CONCLUSION: PPCM patients had increased maternal serum uric acid concentrations. This observation aligns with previous report regarding the increased uric acid concentration in women with preeclampsia and congestive heart failure, suggestive of a common underlying mechanism that mediates the myocardial damage.


Assuntos
Cardiomiopatia Dilatada/sangue , Período Periparto , Vigilância da População , Complicações Cardiovasculares na Gravidez , Ácido Úrico/sangue , Adulto , Biomarcadores/sangue , Cardiomiopatia Dilatada/epidemiologia , Feminino , Humanos , Recém-Nascido , Israel/epidemiologia , Masculino , Gravidez , Prevalência , Prognóstico , Estudos Retrospectivos
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