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1.
BMC Bioinformatics ; 21(1): 377, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883200

RESUMO

BACKGROUND: A large number of experimental studies show that the mutation and regulation of long non-coding RNAs (lncRNAs) are associated with various human diseases. Accurate prediction of lncRNA-disease associations can provide a new perspective for the diagnosis and treatment of diseases. The main function of many lncRNAs is still unclear and using traditional experiments to detect lncRNA-disease associations is time-consuming. RESULTS: In this paper, we develop a novel and effective method for the prediction of lncRNA-disease associations using network feature similarity and gradient boosting (LDNFSGB). In LDNFSGB, we first construct a comprehensive feature vector to effectively extract the global and local information of lncRNAs and diseases through considering the disease semantic similarity (DISSS), the lncRNA function similarity (LNCFS), the lncRNA Gaussian interaction profile kernel similarity (LNCGS), the disease Gaussian interaction profile kernel similarity (DISGS), and the lncRNA-disease interaction (LNCDIS). Particularly, two methods are used to calculate the DISSS (LNCFS) for considering the local and global information of disease semantics (lncRNA functions) respectively. An autoencoder is then used to reduce the dimensionality of the feature vector to obtain the optimal feature parameter from the original feature set. Furthermore, we employ the gradient boosting algorithm to obtain the lncRNA-disease association prediction. CONCLUSIONS: In this study, hold-out, leave-one-out cross-validation, and ten-fold cross-validation methods are implemented on three publicly available datasets to evaluate the performance of LDNFSGB. Extensive experiments show that LDNFSGB dramatically outperforms other state-of-the-art methods. The case studies on six diseases, including cancers and non-cancers, further demonstrate the effectiveness of our method in real-world applications.


Assuntos
Algoritmos , Neoplasias/patologia , RNA Longo não Codificante/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Área Sob a Curva , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/patologia , Humanos , Neoplasias/genética , RNA Longo não Codificante/genética , Curva ROC
2.
PLoS One ; 15(8): e0237387, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790735

RESUMO

Several studies have shown that nutrition and muscle strength were associated with functional recovery in patients with hip fracture. However, the impact of heart failure on the improvement of activity of daily living (ADL) in patients with hip fracture have not been fully investigated. The purpose was investigating the effect of heart failure on the ADL improvement by rehabilitation in patients with hip fracture. A total of 116 patients with hip fracture discharged from our convalescent rehabilitation ward were studied. Heart failure was assessed based on plasma B-type natriuretic peptide (BNP) levels on admission. ADL was assessed based on rehabilitation effectiveness (REs), which was calculated using the FIM instrument. Clinical, demographic, and nutritional variables were measured. Multiple regression analysis was performed with REs as the dependent variable; variables showing significant correlation with REs in univariate analyses were selected as independent variables. Based on plasma BNP levels, we assigned 39 patients to a Low group: 22 (17-25) median (interquartile) pg/mL, 39 to a Middle group: 52 (42-65) pg/mL, and 38 to a High group: 138 (93-209) pg/mL. REs, handgrip strength, Hb, albumin, and GNRI were higher and age was younger in the Low group than High group (each p < 0.01, respectively). Multiple linear regression analysis revealed that age (p < 0.05), sex (p < 0.05), handgrip strength (p < 0.01), FOIS at admission (p < 0.01), rehabilitation time per day (p < 0.01), and BNP (p < 0.05) were significantly associated with REs. The effect of rehabilitation on ADL improvement was significantly blunted in the High group compared to the Low group. In conclusion, these results suggest that heart failure assessed based on plasma BNP levels negatively impacts improvements in ADL achieved through rehabilitation in patients with hip fracture.


Assuntos
Atividades Cotidianas , Insuficiência Cardíaca/patologia , Fraturas do Quadril/fisiopatologia , Peptídeo Natriurético Encefálico/sangue , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Força da Mão , Insuficiência Cardíaca/diagnóstico , Fraturas do Quadril/reabilitação , Humanos , Modelos Lineares , Masculino , Estado Nutricional , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores Sexuais , Resultado do Tratamento
4.
J Cardiovasc Magn Reson ; 22(1): 49, 2020 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600420

RESUMO

BACKGROUND: The right ventricle (RV) often fails when functioning as the systemic ventricle, but the cause is not understood. We tested the hypothesis that myofiber organization is abnormal in the failing systemic right ventricle. METHODS: We used diffusion-weighted cardiovascular magnetic resonance imaging to examine 3 failing hearts explanted from young patients with a systemic RV and one structurally normal heart with postnatally acquired RV hypertrophy for comparison. Diffusion compartment imaging was computed to separate the free diffusive component representing free water from an anisotropic component characterizing the orientation and diffusion characteristics of myofibers. The orientation of each anisotropic compartment was displayed in glyph format and used for qualitative description of myofibers and for construction of tractograms. The helix angle was calculated across the ventricular walls in 5 locations and displayed graphically. Scalar parameters (fractional anisotropy and mean diffusivity) were compared among specimens. RESULTS: The hypertrophied systemic RV has an inner layer, comprising about 2/3 of the wall, composed of hypertrophied trabeculae and an epicardial layer of circumferential myofibers. Myofibers within smaller trabeculae are aligned and organized with parallel fibers while larger, composite bundles show marked disarray, largely between component trabeculae. We observed a narrow range of helix angles in the outer, compact part of the wall consistent with aligned, approximately circumferential fibers. However, there was marked variation of helix angle in the inner, trabecular part of the wall consistent with marked variation in fiber orientation. The apical whorl was disrupted or incomplete and we observed myocardial whorls or vortices at other locations. Fractional anisotropy was lower in abnormal hearts while mean diffusivity was more variable, being higher in 2 but lower in 1 heart, compared to the structurally normal heart. CONCLUSIONS: Myofiber organization is abnormal in the failing systemic RV and might be an important substrate for heart failure and arrhythmia. It is unclear if myofiber disorganization is due to hemodynamic factors, developmental problems, or both.


Assuntos
Imagem de Difusão por Ressonância Magnética , Cardiopatias Congênitas/diagnóstico por imagem , Insuficiência Cardíaca/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Miocárdio/patologia , Miofibrilas/patologia , Disfunção Ventricular Direita/diagnóstico por imagem , Função Ventricular Direita , Adolescente , Pré-Escolar , Feminino , Cardiopatias Congênitas/patologia , Cardiopatias Congênitas/fisiopatologia , Cardiopatias Congênitas/cirurgia , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/cirurgia , Transplante de Coração , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/cirurgia , Humanos , Masculino , Valor Preditivo dos Testes , Disfunção Ventricular Direita/patologia , Disfunção Ventricular Direita/fisiopatologia , Disfunção Ventricular Direita/cirurgia , Adulto Jovem
5.
PLoS One ; 15(7): e0236377, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32702064

RESUMO

INTRODUCTION AND OBJECTIVE: Pro-atrial natriuretic peptide (proANP) and pro-adrenomedullin (proADM) levels increase in acute heart failure and sepsis. After cardiac surgery, children may require increased support in the intensive care unit and may develop complications. The aim of this study was to evaluate the utility of proANP and proADM values, determined prior to cardiac surgery, for predicting the need for increased respiratory or inotropic support during the post-operative period. METHODS: This was a prospective study in children. Biomarkers were analyzed before surgery using a single blood test. The primary endpoints were the need for greater respiratory and/or inotropic support during the post-operative period. Secondary endpoints were the relationship between these biomarkers and complications after surgery. RESULTS: One hundred thirteen patients were included. ProANP and proADM were higher in children who required greater respiratory and inotropic support, especially proANP; for increased respiratory support, 578.9 vs. 106.6 pmol/L (p = 0.004), and for increased inotropic support, 1938 vs. 110.4 pmol/L (p = 0.002). ProANP had a greater AUC than proADM for predicting increased respiratory support after surgery: 0.791 vs. 0.724. A possible cut-off point for proANP could be ≥ 325 pmol/L (sensitivity = 66.7% and specificity = 88.8%). In the multivariate analysis, the logarithmic transformation of proANP was independently associated with the need for increased respiratory support (OR = 3.575). Patients who presented a poor outcome after cardiac surgery also had higher biomarker values (proADM, p = 0.013; proANP, p = 0.001). CONCLUSIONS: Elevated proANP before cardiac surgery may identify which children will need more respiratory and inotropic support during the post-operative period.


Assuntos
Adrenomedulina/sangue , Fator Natriurético Atrial/sangue , Biomarcadores/sangue , Insuficiência Cardíaca/sangue , Procedimentos Cirúrgicos Cardíacos , Criança , Pré-Escolar , Feminino , Coração/fisiopatologia , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/cirurgia , Humanos , Lactente , Recém-Nascido , Masculino , Pediatria , Cirurgia Torácica
6.
PLoS One ; 15(7): e0236827, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730362

RESUMO

BACKGROUND: Heart failure (HF) is a major cause of morbidity and mortality. However, much of the clinical data is unstructured in the form of radiology reports, while the process of data collection and curation is arduous and time-consuming. PURPOSE: We utilized a machine learning (ML)-based natural language processing (NLP) approach to extract clinical terms from unstructured radiology reports. Additionally, we investigate the prognostic value of the extracted data in predicting all-cause mortality (ACM) in HF patients. MATERIALS AND METHODS: This observational cohort study utilized 122,025 thoracoabdominal computed tomography (CT) reports from 11,808 HF patients obtained between 2008 and 2018. 1,560 CT reports were manually annotated for the presence or absence of 14 radiographic findings, in addition to age and gender. Thereafter, a Convolutional Neural Network (CNN) was trained, validated and tested to determine the presence or absence of these features. Further, the ability of CNN to predict ACM was evaluated using Cox regression analysis on the extracted features. RESULTS: 11,808 CT reports were analyzed from 11,808 patients (mean age 72.8 ± 14.8 years; 52.7% (6,217/11,808) male) from whom 3,107 died during the 10.6-year follow-up. The CNN demonstrated excellent accuracy for retrieval of the 14 radiographic findings with area-under-the-curve (AUC) ranging between 0.83-1.00 (F1 score 0.84-0.97). Cox model showed the time-dependent AUC for predicting ACM was 0.747 (95% confidence interval [CI] of 0.704-0.790) at 30 days. CONCLUSION: An ML-based NLP approach to unstructured CT reports demonstrates excellent accuracy for the extraction of predetermined radiographic findings, and provides prognostic value in HF patients.


Assuntos
Insuficiência Cardíaca/mortalidade , Processamento de Imagem Assistida por Computador/métodos , Processamento de Linguagem Natural , Redes Neurais de Computação , Radiografia Abdominal/métodos , Radiografia Torácica/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Estudos de Coortes , Registros Eletrônicos de Saúde , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/patologia , Humanos , Aprendizado de Máquina , Masculino , Prognóstico , Taxa de Sobrevida
7.
Cardiovasc Ther ; 2020: 2016259, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32528555

RESUMO

Background: Myocardial infarction (MI) was a severe cardiovascular disease resulted from acute, persistent hypoxia, or ischemia condition. Additionally, MI generally led to heart failure, even sudden death. A multitude of research studies proposed that long noncoding RNAs (lncRNAs) frequently participated in the regulation of heart diseases. The specific function and molecular mechanism of SOX2-OT in MI remained unclear. Aim of the Study. The current research was aimed to explore the role of SOX2-OT in MI. Methods: Bioinformatics analysis (DIANA tools and Targetscan) and a wide range of experiments (CCK-8, flow cytometry, RT-qPCR, luciferase reporter, RIP, caspase-3 activity, trans-well, and western blot assays) were adopted to investigate the function and mechanism of SOX2-OT. Results: We discovered that hypoxia treatment decreased cell viability but increased cell apoptosis. Besides, lncRNA SOX2-OT expression was upregulated in hypoxic HCMs. Hereafter, we confirmed that SOX2-OT could negatively regulate miR-27a-3p levels by directly binding with miR-27a-3p, and miR-27a-3p also could negatively regulate SOX2-OT levels. Furthermore, knockdown of SOX2-OT promoted cell proliferation, migration, and invasion, but limited cell apoptosis. However, these effects were reversed by anti-miR-27a-5p. Besides, we verified that miR-27a-3p binding with the 3'UTR of TGFBR1 and SOX2-OT regulated TGFßR1 level by collaborating with miR-27a-3p in HCMs. Eventually, rescue assays validated that the influence of SOX2-OT silence or miR-27a-3p overexpression on cellular processes in cardiomyocytes injury was counteracted by TGFBR1 overexpression. Conclusions: Long noncoding RNA SOX2-OT exacerbated hypoxia-induced cardiomyocytes injury by regulating miR-27a-3p/TGFßR1 axis, which may provide a novel insight for heart failure treatment.


Assuntos
Insuficiência Cardíaca/metabolismo , MicroRNAs/metabolismo , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , RNA Longo não Codificante/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Apoptose , Hipóxia Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Regulação da Expressão Gênica , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/patologia , Humanos , MicroRNAs/genética , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Miócitos Cardíacos/patologia , RNA Longo não Codificante/genética , Receptor do Fator de Crescimento Transformador beta Tipo I/genética , Transdução de Sinais
8.
PLoS One ; 15(6): e0234913, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32574189

RESUMO

The transcriptional regulatory machinery in mitochondrial bioenergetics is complex and is still not completely understood. We previously demonstrated that the histone methyltransferase Smyd1 regulates mitochondrial energetics. Here, we identified Perm1 (PPARGC-1 and ESRR-induced regulator, muscle specific 1) as a downstream target of Smyd1 through RNA-seq. Chromatin immunoprecipitation assay showed that Smyd1 directly interacts with the promoter of Perm1 in the mouse heart, and this interaction was significantly reduced in mouse hearts failing due to pressure overload for 4 weeks, where Perm1 was downregulated (24.4 ± 5.9% of sham, p<0.05). Similarly, the Perm1 protein level was significantly decreased in patients with advanced heart failure (55.2 ± 13.1% of donors, p<0.05). Phenylephrine (PE)-induced hypertrophic stress in cardiomyocytes also led to downregulation of Perm1 (55.7 ± 5.7% of control, p<0.05), and adenovirus-mediated overexpression of Perm1 rescued PE-induced downregulation of estrogen-related receptor alpha (ERRα), a key transcriptional regulator of mitochondrial energetics, and its target gene, Ndufv1 (Complex I). Pathway enrichment analysis of cardiomyocytes in which Perm1 was knocked-down by siRNA (siPerm1), revealed that the most downregulated pathway was metabolism. Cell stress tests using the Seahorse XF analyzer showed that basal respiration and ATP production were significantly reduced in siPerm1 cardiomyocytes (40.7% and 23.6% of scrambled-siRNA, respectively, both p<0.05). Luciferase reporter gene assay further revealed that Perm1 dose-dependently increased the promoter activity of the ERRα gene and known target of ERRα, Ndufv1 (Complex I). Overall, our study demonstrates that Perm1 is an essential regulator of cardiac energetics through ERRα, as part of the Smyd1 regulatory network.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Proteínas Musculares/metabolismo , Miocárdio/metabolismo , Fatores de Transcrição/metabolismo , Adulto , Idoso , Animais , Metilação de DNA , Modelos Animais de Doenças , Regulação para Baixo , Complexo I de Transporte de Elétrons/genética , Metabolismo Energético/genética , Feminino , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/cirurgia , Transplante de Coração , Histonas/genética , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas Musculares/genética , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Fosforilação Oxidativa , Fenilefrina/farmacologia , Cultura Primária de Células , Regiões Promotoras Genéticas/genética , RNA Interferente Pequeno/metabolismo , RNA-Seq , Ratos , Receptores Estrogênicos/genética
9.
Int J Cardiovasc Imaging ; 36(10): 2027-2038, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32533279

RESUMO

In patients with heart failure with preserved ejection fraction (HFpEF), diabetes mellitus (DM) and obesity are important comorbidities as well as major risk factors. Their conjoint impact on the myocardium provides insight into the HFpEF aetiology. We sought to investigate the association between obesity, DM, and their combined effect on alterations in the myocardial tissue in HFpEF patients. One hundred and sixty-two HFpEF patients (55 ± 12 years, 95 men) and 45 healthy subjects (53 ± 12 years, 27 men) were included. Patients were classified according to comorbidity prevalence (36 obese patients without DM, 53 diabetic patients without obesity, and 73 patients with both). Myocardial remodeling, fibrosis, and longitudinal contractility were quantified with cardiovascular magnetic resonance imaging using cine and myocardial native T1 images. Patients with DM and obesity had impaired global longitudinal strain (GLS) and increased myocardial native T1 compared to patients with only one comorbidity (DM + Obesity vs. DM and Obesity; GLS, - 15 ± 2.1 vs - 16.5 ± 2.4 and - 16.7 ± 2.2%; native T1, 1162 ± 37 vs 1129 ± 25 and 1069 ± 29 ms; P < 0.0001 for all). A negative synergistic effect of combined obesity and DM prevalence was observed for native T1 (np2 = 0.273, p = 0.002) and GLS (np2 = 0.288, p < 0.0001). Additionally, severity of insulin resistance was associated with GLS (R = 0.590, P < 0.0001), and native T1 (R = 0.349, P < 0.0001). The conjoint effect of obesity and DM in HFpEF patients is associated with diffuse myocardial fibrosis and deterioration in GLS. The negative synergistic effects observed on the myocardium may be related to severity of insulin resistance.


Assuntos
Diabetes Mellitus/fisiopatologia , Insuficiência Cardíaca/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Miocárdio/patologia , Obesidade/fisiopatologia , Volume Sistólico , Função Ventricular Esquerda , Adulto , Idoso , Boston/epidemiologia , Comorbidade , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Feminino , Fibrose , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Contração Miocárdica , Obesidade/diagnóstico , Obesidade/epidemiologia , Valor Preditivo dos Testes , Prevalência , Estudos Retrospectivos , Fatores de Risco , Remodelação Ventricular
10.
Cardiovasc Ther ; 2020: 8584763, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32426037

RESUMO

Background: Although many studies have been performed to elucidate the molecular mechanisms of heart failure, an effective pharmacological therapy to protect cardiac tissues from severe loss of contractile function associated with heart failure after acute myocardial infarction (MI) has yet to be developed. Methods: We examined the cardioprotective effects of (Z)-2-acetoxy-3-(3,4-dihydroxyphenyl) acrylic acid, a new compound with potent antioxidant and antiapoptotic activities in a rat model of heart failure. (Z)-2-Acetoxy-3-(3,4-dihydroxyphenyl) acrylic acid was systemically delivered to rats 6 weeks after MI at different doses (15, 30, and 60 mg/kg). Cardiac function was assessed by hemodynamic measurements. The expression of proinflammatory cytokines, apoptosis-related molecules, and markers of adverse ventricular remodeling was measured using RT-PCR and Western blot. Results: Treatment with (Z)-2-acetoxy-3-(3,4-dihydroxyphenyl) acrylic acid significantly improved cardiac function, in particular by increasing dP/dt. Simultaneously, the expression of the proinflammatory cytokines TNF-α and IL-1ß was markedly reduced in the treatment group compared with the MI group. In addition, (Z)-2-acetoxy-3-(3,4-dihydroxyphenyl) acrylic acid-treated tissues displayed decreased expression of Bax, caspase-3, and caspase-9 and increased expression of Bcl-2, which was in part due to the promotion of Akt phosphorylation. Conclusion: These data demonstrated that (Z)-2-acetoxy-3-(3,4-dihydroxyphenyl) acrylic acid possesses potent cardioprotective effects against cardiac injury in a rat model of heart failure, which is mediated, at least in part, by suppression of the inflammatory and cell apoptosis responses.


Assuntos
Acrilatos/farmacologia , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Infarto do Miocárdio/complicações , Miócitos Cardíacos/efeitos dos fármacos , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Modelos Animais de Doenças , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Mediadores da Inflamação/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Masculino , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos
12.
Curr Cardiol Rev ; 16(3): 202-211, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32351188

RESUMO

Heart Failure (HF) represents a leading cause of morbidity and mortality worldwide. Despite the recent advances in the treatment of this condition, patients´ prognosis remains unfavorable in most cases. Sacubitril/valsartan and ivabradine have been recently approved to improve clinical outcomes in patients with HF with reduced ejection fraction. Drugs under investigation for treating patients with HF encompass many novel mechanisms including vasoactive peptides, blocking inflammatory- mediators, natriuretic peptides, selective non-steroidal mineralocorticoid-receptor antagonists, myocardial ß3 adrenoreceptor agonists, inhibiting the cytochrome C/cardiolipin peroxidase complex, neuregulin-1/ErbB signaling and inhibiting late inward sodium current. The aim of this manuscript is to review the main drugs under investigation for the treatment of patients with HF and give perspectives for their implementation into clinical practice.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Idoso , Insuficiência Cardíaca/patologia , Humanos , Pessoa de Meia-Idade
13.
J Pharmacol Sci ; 143(3): 199-208, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32414690

RESUMO

The optimum strategy for heart failure (HF) treatment has yet to be elucidated. This study intended to test the benefit of a combination of valsartan (VAL) and perifosine (PER), a specific AKT inhibitor, in protecting against pressure overload induced mouse HF. Mouse were subjected to aortic banding (AB) surgery to establish HF models and then were given vehicle (HF), VAL (50 mg/kg/d), PER (30 mg/kg/d) or combination of VAL and PER for 4 weeks. Mouse with sham surgery treated with VEH were used for control (VEH). VAL or PER treatment could significantly alleviate mouse heart weight, attenuate cardiac fibrosis and improve cardiac function. The combination treatment of VAL and PER presented much better benefit compared with VAL or PER group respectively. PER treatment significantly inhibited AKT/GSK3ß/mTORC1 signaling. Besides the classic AT1 inhibition, VAL treatment significantly inhibited MAPK (ERK1/2) signaling. Furthermore, VAL and PER treatment could markedly prevent neonatal rat cardiomyocyte hypertrophy and the activation of neonatal rat cardiac fibroblast. Combination of VAL and PER also presented superior beneficial effects than single treatment of VAL or PER in vitro experiments respectively. This study presented that the combination of valsartan and PER may be a potential treatment for HF prevention.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/prevenção & controle , Fosforilcolina/análogos & derivados , Pressão/efeitos adversos , Valsartana/administração & dosagem , Animais , Modelos Animais de Doenças , Quimioterapia Combinada , Glicogênio Sintase Quinase 3 beta/metabolismo , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Tamanho do Órgão , Fosforilcolina/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
Cardiovasc Pathol ; 48: 107218, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32388447

RESUMO

Cardiac amyloid A (AA) amyloidosis is rare. We present the case of a 72-year-old woman with obstructive hypertrophic cardiomyopathy (HCM) and biopsy-proven renal AA amyloidosis whose dyspnea and exercise intolerance had worsened over the previous year. Her AA amyloidosis was suspected to be secondary to chronic diverticulitis for which she had undergone hemicolectomy and sigmoidectomy 3 years prior. Echocardiographic findings were consistent with worsening left ventricular outflow tract obstruction at rest. Cardiac magnetic resonance imaging revealed patchy areas of midwall late gadolinium enhancement. Right ventricular endomyocardial biopsy did not reveal amyloid deposition, and cardiac technetium-99m pyrophosphate scintigraphy did not suggest transthyretin amyloidosis. The patient underwent septal myectomy with resection of an accessory papillary muscle. Pathological examination of the myectomy specimen was consistent with HCM. In addition, there was a thick layer of diffuse endocardial and vascular amyloid deposition that was identified as AA type by laser-microdissection with liquid chromatography-coupled tandem-mass spectrometry. This case report highlights the presence of 2 distinct disease processes occurring simultaneously and the importance of tissue diagnosis of AA amyloidosis, a condition that is not commonly associated with HCM.


Assuntos
Amiloidose/complicações , Cardiomiopatia Hipertrófica/complicações , Insuficiência Cardíaca/etiologia , Nefropatias/complicações , Miocárdio/patologia , Obstrução do Fluxo Ventricular Externo/etiologia , Idoso , Amiloidose/metabolismo , Amiloidose/patologia , Amiloidose/fisiopatologia , Procedimentos Cirúrgicos Cardíacos , Cardiomiopatia Hipertrófica/metabolismo , Cardiomiopatia Hipertrófica/patologia , Cardiomiopatia Hipertrófica/fisiopatologia , Feminino , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Nefropatias/metabolismo , Nefropatias/patologia , Miocárdio/metabolismo , Proteína Amiloide A Sérica/metabolismo , Resultado do Tratamento , Função Ventricular Esquerda , Obstrução do Fluxo Ventricular Externo/metabolismo , Obstrução do Fluxo Ventricular Externo/patologia , Obstrução do Fluxo Ventricular Externo/fisiopatologia
15.
Virchows Arch ; 477(4): 603-607, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32372222

RESUMO

Three cases of unexpected/sudden death (N = 2) or acute heart failure (N = 1) were investigated in our centre. The first patient died unexpectedly after surgery for cardiac tamponade and constrictive pericarditis; at autopsy, gross features mimicked a pericardial mesothelioma. The second patient died suddenly after recovering from a respiratory insufficiency episode; autopsy revealed an epicardial mass encircling the right coronary artery. The third patient presenting symptoms mimicked a fulminant myocarditis and she underwent endomyocardial biopsy. In all cases, histology disclosed a diffuse large B cell non-Hodgkin lymphoma, localized to the pericardium together with the right ventricle and the conduction system, to the epicardium and the right coronary artery or to the myocardium, respectively. Histology was crucial for the diagnosis, the atypical presentation favouring other diagnostic hypotheses. Although primary cardiac lymphoma is uncommon and usually shows a sub-acute onset, it may also cause unexpected/sudden death or acute heart failure.


Assuntos
Morte Súbita Cardíaca/etiologia , Insuficiência Cardíaca/etiologia , Neoplasias Cardíacas/complicações , Linfoma Difuso de Grandes Células B/complicações , Miocárdio/patologia , Doença Aguda , Idoso , Autopsia , Biomarcadores Tumorais/análise , Biópsia , Causas de Morte , Morte Súbita Cardíaca/patologia , Evolução Fatal , Feminino , Insuficiência Cardíaca/patologia , Neoplasias Cardíacas/imunologia , Neoplasias Cardíacas/patologia , Humanos , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Miocárdio/imunologia
16.
Basic Res Cardiol ; 115(3): 31, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: covidwho-46686

RESUMO

From January 2020, coronavirus disease (COVID-19) originated in China has spread around the world. The disease is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The presence of myocarditis, cardiac arrest, and acute heart failure in COVID-19 patients suggests the existence of a relationship between SARS-CoV-2 infection and cardiac disease. The Notch signalling is a major regulator of cardiovascular function and it is also implicated in several biological processes mediating viral infections. In this report we discuss the possibility to target Notch signalling to prevent SARS-CoV-2 infection and interfere with the progression of COVID-19- associated heart and lungs disease.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Cardiopatias/tratamento farmacológico , Cardiopatias/etiologia , Pneumopatias/tratamento farmacológico , Pneumopatias/etiologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/fisiopatologia , Receptores Notch/antagonistas & inibidores , Proteína ADAM17/antagonistas & inibidores , Betacoronavirus/efeitos dos fármacos , China , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Progressão da Doença , Furina/metabolismo , Parada Cardíaca/etiologia , Parada Cardíaca/patologia , Cardiopatias/patologia , Cardiopatias/fisiopatologia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/patologia , Humanos , Interleucina-6/imunologia , Pneumopatias/patologia , Pneumopatias/fisiopatologia , Miocardite/etiologia , Miocardite/patologia , Pandemias , Peptidil Dipeptidase A/deficiência , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Receptores Notch/metabolismo , Transdução de Sinais/efeitos dos fármacos
17.
Eur J Heart Fail ; 22(5): 911-915, 2020 05.
Artigo em Inglês | MEDLINE | ID: covidwho-46118

RESUMO

We describe the first case of acute cardiac injury directly linked to myocardial localization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a 69-year-old patient with flu-like symptoms rapidly degenerating into respiratory distress, hypotension, and cardiogenic shock. The patient was successfully treated with venous-arterial extracorporeal membrane oxygenation (ECMO) and mechanical ventilation. Cardiac function fully recovered in 5 days and ECMO was removed. Endomyocardial biopsy demonstrated low-grade myocardial inflammation and viral particles in the myocardium suggesting either a viraemic phase or, alternatively, infected macrophage migration from the lung.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Coração/virologia , Miocardite/virologia , Pneumonia Viral/complicações , Choque Cardiogênico/terapia , Choque Cardiogênico/virologia , Idoso , Biópsia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Oxigenação por Membrana Extracorpórea , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/virologia , Humanos , Masculino , Miocardite/patologia , Miocárdio/patologia , Pandemias , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Respiração Artificial , Choque Cardiogênico/etiologia , Choque Cardiogênico/patologia
18.
Basic Res Cardiol ; 115(3): 31, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32274570

RESUMO

From January 2020, coronavirus disease (COVID-19) originated in China has spread around the world. The disease is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The presence of myocarditis, cardiac arrest, and acute heart failure in COVID-19 patients suggests the existence of a relationship between SARS-CoV-2 infection and cardiac disease. The Notch signalling is a major regulator of cardiovascular function and it is also implicated in several biological processes mediating viral infections. In this report we discuss the possibility to target Notch signalling to prevent SARS-CoV-2 infection and interfere with the progression of COVID-19- associated heart and lungs disease.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Cardiopatias/tratamento farmacológico , Cardiopatias/etiologia , Pneumopatias/tratamento farmacológico , Pneumopatias/etiologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/fisiopatologia , Receptores Notch/antagonistas & inibidores , Proteína ADAM17/antagonistas & inibidores , Betacoronavirus/efeitos dos fármacos , China , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Progressão da Doença , Furina/metabolismo , Parada Cardíaca/etiologia , Parada Cardíaca/patologia , Cardiopatias/patologia , Cardiopatias/fisiopatologia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/patologia , Humanos , Interleucina-6/imunologia , Pneumopatias/patologia , Pneumopatias/fisiopatologia , Miocardite/etiologia , Miocardite/patologia , Pandemias , Peptidil Dipeptidase A/deficiência , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Receptores Notch/metabolismo , Transdução de Sinais/efeitos dos fármacos
19.
Rev. chil. cardiol ; 39(1): 24-33, abr. 2020. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1115446

RESUMO

INTRODUCCIÓN: Los ratones SR-B1 KO/ApoER6 1h/h que son alimentados con una dieta rica en grasas saturadas, desarrollan enfermedad coronaria aterosclerótica severa, complicaciones isquémicas e insuficiencia cardíaca, con alta mortalidad. Los estudios con este modelo se han enfocado fundamentalmente en la enfermedad coronaria y menos en el remodelado cardíaco. El OBJETIVO del trabajo ha sido caracterizar el remodelado miocárdico, evaluar la evolución temporal de la función ventricular izquierda y la sobrevida asociada a enfermedad cardíaca por ateromatosis. MÉTODO: Ratones homocigotos SR-B1 KO/ApoER6 1h/h fueron alimentados por 8 semanas con dieta aterogénica o dieta normal y se comparó la sobrevida en ambos grupos. A las 4 semanas se realizó un ecocardiograma bidimensional. En los ratones eutanasiados se evaluó en la pared cardíaca fibrosis miocárdica y tamaño de los cardiomiocitos por morfometría, apoptosis con técnica de TUNEL e infiltración por células inflamatorias mononucleares (ED1) por inmunohistoquímica. RESULTADOS: En el grupo que recibió dieta aterogénica la sobrevida se redujo en 46,7% (p < 0.001), debido a muerte súbita y a falla cardíaca progresiva. En este grupo, a las 4 semanas se observó dilatación de cavidades izquierdas y disminución de la fracción de eyección del ventrículo izquierdo en comparación con el grupo control (79,3 ± 1,3% vs 66 ± 3,7%, p<0,01). También se observó aumento de la masa cardíaca relativa de 2.1 veces (p<0,001) y del peso pulmonar relativo en 80% (p<0,001), sin cambios en las dimensiones de los cardiomiocitos. En el miocardio de los ratones que recibieron dieta aterogénica hubo un aumento de la fibrosis cardíaca de 7.9 veces (p < 0.01) y del número de cardiomiocitos apoptóticos en 55.9 veces (p < 0.01), junto a un aumento del número de células inflamatorias mononucleares ED1. CONCLUSIONES: En el modelo de falla cardíaca severa de etiología isquémica con alta mortalidad en el ratón homocigoto SR-B1 KO/ApoER6 1h/h sometido a una dieta aterogénica, con falla cardíaca izquierda por disfunción sistólica, el remodelado patológico del miocardio está dado fundamentalmente por apoptosis y fibrosis. También se observa un aumento discreto de macrófagos en la pared cardíaca. Es posible que el edema parietal también pueda ser un mecanismo de remodelado relevante en este modelo.


Abstract: SR-B1 KO/ApoER6 1h/h mice fed a high saturated fat diet develop severe coronary atheromatosis, and cardiac failure with a high mortality rate. Cardiac remodeling under these conditions has not been well studied. AIM: To evaluate the time course of left ventricular function, cardiac remodeling and survival associated to the administration of an atherogenic diet. METHOD: Homozygote SR-B1 KO/ApoER6 1h/h mice received an atherogenic diet for 8 weeks. Mice receiving a normal diet served as controls. Survival rate, myocardial fibrosis, cardiomyocyte size, apoptosis and infiltration by inflammatory or mononuclear cells were compared between groups. A TUNEL technique was used to evaluate apoptosis. RESULTS: A 46.7% survival reduction compared to controls was observed in the experimental group (p<0.01), due to left ventricular and atrial dilatation associated to a decrease in ejection fraction (79,3 ± 1,3% vs 66 ± 3,7%, p<0,01, respectively). Also, an increased cardiac weight, 2.6 times greater was observed in the experimental group, compared to controls. Mice receiving the atherogenic diet showed an 80% increased lung weight. There was no evident change in cardiomyocytes, but there was more (7.9 times) cardiac fibrosis (p<0.01) and 55.9 times more apoptotic cells. (p<0.01), along with a greater number of inflammatory cells and ED1 mononuclear cells. CONCLUSION: Mice receiving an atherogenic diet develop heart failure and reduced survival rate. This is associated with cardiac remodeling with underlying apoptosis an ventricular wall fibrosis. It is posible that wall edema might contribute to the observed cardiac remodeling.


Assuntos
Animais , Camundongos , Remodelação Ventricular , Dieta Aterogênica , Insuficiência Cardíaca/etiologia , Hiperlipidemias/patologia , Isquemia/etiologia , Fibrose , Análise de Sobrevida , Função Ventricular Esquerda , Apoptose , Camundongos Knockout , Disfunção Ventricular , Modelos Animais de Doenças , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/patologia , Isquemia/fisiopatologia , Isquemia/mortalidade , Isquemia/patologia
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