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[PMID]:28747397
[Au] Autor:Gao H; Aderhold A; Mangion K; Luo X; Husmeier D; Berry C
[Ad] Endereço:School of Mathematics and Statistics, University of Glasgow, Glasgow, UK hao.gao@glasgow.ac.uk.
[Ti] Título:Changes and classification in myocardial contractile function in the left ventricle following acute myocardial infarction.
[So] Source:J R Soc Interface;14(132), 2017 Jul.
[Is] ISSN:1742-5662
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In this research, we hypothesized that novel biomechanical parameters are discriminative in patients following acute ST-segment elevation myocardial infarction (STEMI). To identify these biomechanical biomarkers and bring computational biomechanics 'closer to the clinic', we applied state-of-the-art multiphysics cardiac modelling combined with advanced machine learning and multivariate statistical inference to a clinical database of myocardial infarction. We obtained data from 11 STEMI patients (ClinicalTrials.gov NCT01717573) and 27 healthy volunteers, and developed personalized mathematical models for the left ventricle (LV) using an immersed boundary method. Subject-specific constitutive parameters were achieved by matching to clinical measurements. We have shown, for the first time, that compared with healthy controls, patients with STEMI exhibited increased LV wall active tension when normalized by systolic blood pressure, which suggests an increased demand on the contractile reserve of remote functional myocardium. The statistical analysis reveals that the required patient-specific contractility, normalized active tension and the systolic myofilament kinematics have the strongest explanatory power for identifying the myocardial function changes post-MI. We further observed a strong correlation between two biomarkers and the changes in LV ejection fraction at six months from baseline (the required contractility ( = - 0.79, < 0.01) and the systolic myofilament kinematics ( = 0.70, = 0.02)). The clinical and prognostic significance of these biomechanical parameters merits further scrutinization.
[Mh] Termos MeSH primário: Ventrículos do Coração/fisiopatologia
Contração Miocárdica/fisiologia
Infarto do Miocárdio/fisiopatologia
Função Ventricular
[Mh] Termos MeSH secundário: Adulto
Idoso
Estudos de Casos e Controles
Feminino
Ventrículos do Coração/patologia
Seres Humanos
Masculino
Meia-Idade
Infarto do Miocárdio/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170728
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE


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[PMID]:29337067
[Au] Autor:Yassa ME; Mansour IA; Sewelam NI; Hamza H; Gaafar T
[Ad] Endereço:Department of Clinical and Chemical Pathology, Kasr Al-Ainy School of Medicine, Cairo University, Kasr Al-Ainy St., 11562, Cairo, Egypt. Electronic address: marianne.yassa@kasralainy.edu.eg.
[Ti] Título:The impact of growth factors on human induced pluripotent stem cells differentiation into cardiomyocytes.
[So] Source:Life Sci;196:38-47, 2018 Mar 01.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Human induced pluripotent stem cells (hiPSCs) act as a promising therapeutic alternative for cardiovascular diseases. They yield a large number of functional cardiomyocytes (CMs) from autologous cell sources without ethical or immunological problems. However, significant limitations still remain in terms of line-to-line variability in CM yield and reproducibility. AIM: To efficiently enhance NP0040 hiPSCs differentiation into CMs. MAIN METHODS: Following a standard cardiac differentiation protocol using small molecules targeting the canonical Wnt signaling, growth factors (BMP4 and FGF2) and ascorbic acid were added further in order to increase the cardiac differentiation efficiency. All cultures were conducted in serum-free, feeder-free monolayer system followed by lactate purification. KEY FINDINGS: Using NP0040 hiPSCs, the CM yield resulting from modulation of the Wnt signaling pathway alone was inefficient compared to previous studies while the addition of BMP4, FGF2 and ascorbic acid resulted in enhanced cardiac differentiation outcome. The later resulted in a high yield (up to 92%) of cardiac troponin-T (cTnT) + CMs contracting spontaneously as organized sheets in 15 independent experiments. They were validated structurally and functionally using immunofluorescent staining for sarcomeric α-actinin, cTnT, MLC2v and Connexin 43. Reverse-transcriptase PCR revealed cardiac transcription factors and cardiac-specific genes expression. CMs were electrically connected to one another. Recorded action potential (AP) showed waves of relatively mature ventricular-like phenotype. SIGNIFICANCE: We demonstrated that hiPSC lines respond differently to a standard cardiac differentiation protocol and that a well-orchestrated interplay between Wnt, BMP4, FGF/MEK and Ascorbic acid MEK/ERK1/2 signaling pathways is beneficial in enhancing the differentiation outcome.
[Mh] Termos MeSH primário: Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos
Peptídeos e Proteínas de Sinalização Intercelular/farmacologia
Miócitos Cardíacos/efeitos dos fármacos
[Mh] Termos MeSH secundário: Potenciais de Ação/efeitos dos fármacos
Ácido Ascórbico/farmacologia
Proteína Morfogenética Óssea 4/metabolismo
Diferenciação Celular/efeitos dos fármacos
Espaço Extracelular/efeitos dos fármacos
Expressão Gênica/efeitos dos fármacos
Glucose/deficiência
Seres Humanos
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
Contração Miocárdica
Miócitos Cardíacos/metabolismo
Troponina T/metabolismo
Vitaminas/farmacologia
Via de Sinalização Wnt/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bone Morphogenetic Protein 4); 0 (Intercellular Signaling Peptides and Proteins); 0 (Troponin T); 0 (Vitamins); IY9XDZ35W2 (Glucose); PQ6CK8PD0R (Ascorbic Acid)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE


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[PMID]:29342222
[Au] Autor:Amar A; Zlochiver S; Barnea O
[Ad] Endereço:Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel.
[Ti] Título:Mechano-electric feedback effects in a three-dimensional (3D) model of the contracting cardiac ventricle.
[So] Source:PLoS One;13(1):e0191238, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mechano-electric feedback affects the electrophysiological and mechanical function of the heart and the cellular, tissue, and organ properties. To determine the main factors that contribute to this effect, this study investigated the changes in the action potential characteristics of the ventricle during contraction. A model of stretch-activated channels was incorporated into a three-dimensional multiscale model of the contracting ventricle to assess the effect of different preload lengths on the electrophysiological behavior. The model describes the initiation and propagation of the electrical impulse, as well as the passive (stretch) and active (contraction) changes in the cardiac mechanics. Simulations were performed to quantify the relationship between the cellular activation and recovery patterns as well as the action potential durations at different preload lengths in normal and heart failure pathological conditions. The simulation results showed that heart failure significantly affected the excitation propagation parameters compared to normal condition. The results showed that the mechano-electrical feedback effects appear to be most important in failing hearts with low ejection fraction.
[Mh] Termos MeSH primário: Modelos Cardiovasculares
Contração Miocárdica/fisiologia
[Mh] Termos MeSH secundário: Animais
Fenômenos Biomecânicos
Simulação por Computador
Fenômenos Eletrofisiológicos
Retroalimentação Fisiológica
Insuficiência Cardíaca/patologia
Insuficiência Cardíaca/fisiopatologia
Ventrículos do Coração/anatomia & histologia
Seres Humanos
Imagem Tridimensional
Função Ventricular
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191238


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[PMID]:29174818
[Au] Autor:Pei Z; Deng Q; Babcock SA; He EY; Ren J; Zhang Y
[Ad] Endereço:The Second Department of Cardiology, The Third Hospital of Nanchang, Nanchang, Jiangxi 330009, China.
[Ti] Título:Inhibition of advanced glycation endproduct (AGE) rescues against streptozotocin-induced diabetic cardiomyopathy: Role of autophagy and ER stress.
[So] Source:Toxicol Lett;284:10-20, 2018 Mar 01.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Diabetes mellitus leads to oxidative stress and contractile dysfunction in the heart. Although several rationales have been speculated, the precise mechanism behind diabetic cardiomyopathy remains elusive. This study was designed to assess the role of inhibition of advanced glycation endproducts (AGE) in streptozotocin (STZ)-induced diabetic cardiac dysfunction. Cardiac contractile function was assessed in normal C57BL/6 and STZ (200mg/kg, single injection and maintained for 2 wks)-induced diabetic mice treated with or without the AGE inhibitor aminoguanidine (50mg/kg/d in drinking water) for 2 weeks using echocardiography and IonOptix MyoCam techniques. Diabetes compromised cardiac contractile function shown as reduced fractional shortening and ejection fraction, enlarged left ventricular end systolic/diastolic diameters, decreased peak shortening, maximal velocity of shortening/relengthening, prolonged shortening and relengthening duration as well as impaired intracellular Ca homeostasis, the effects of which were alleviated or reversed by aminoguanidine treatment. Diabetes also inhibited autophagy, increased ER stress and phosphorylation of pro-hypertrophic signaling molecules Akt and mTOR, the effect of which was reversed by aminoguanidine. In vitro study revealed that methylglyoxal-derived AGE (MG-AGE) incubation in isolated cardiomyocytes promoted oxidation of sarco(endo)plasmic reticulum Ca -ATPase (SERCA2a) and production of superoxide, the effects of which were negated by the autophagy inducer rapamycin, the ER stress chaperone TUDCA or the antioxidant N-acetylcysteine. Taken together, these data revealed that inhibition of AGE formation rescues against experimental diabetes-induced cardiac remodeling and contractile dysfunction possible through regulation of autophagy and ER stress.
[Mh] Termos MeSH primário: Autofagia/efeitos dos fármacos
Diabetes Mellitus Experimental/metabolismo
Cardiomiopatias Diabéticas/prevenção & controle
Estresse do Retículo Endoplasmático/efeitos dos fármacos
Produtos Finais de Glicação Avançada/antagonistas & inibidores
Guanidinas/farmacologia
[Mh] Termos MeSH secundário: Animais
Cálcio/metabolismo
Diabetes Mellitus Experimental/patologia
Cardiomiopatias Diabéticas/metabolismo
Cardiomiopatias Diabéticas/patologia
Ecocardiografia
Masculino
Camundongos Endogâmicos C57BL
Contração Miocárdica/efeitos dos fármacos
Miócitos Cardíacos/efeitos dos fármacos
Estreptozocina
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glycation End Products, Advanced); 0 (Guanidines); 5W494URQ81 (Streptozocin); SCQ4EZQ113 (pimagedine); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE


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[PMID]:29217190
[Au] Autor:Unuma K; Aki T; Nagano S; Watanabe R; Uemura K
[Ad] Endereço:Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
[Ti] Título:The down-regulation of cardiac contractile proteins underlies myocardial depression during sepsis and is mitigated by carbon monoxide.
[So] Source:Biochem Biophys Res Commun;495(2):1668-1674, 2018 01 08.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The aim of this study is to investigate the mechanism underling cardiac dysfunction during sepsis, as well as the possible amelioration of this dysfunction by exogenous carbon monoxide (CO) administration. For this purpose, rats (six-week-old, male, Sprague-Dawley) were administered LPS (15 mg/kg body weight, i.p. 6 h) and/or CORM (30 mg/kg, i.p.). The decreased left ventricular ejection fraction (EF) observed in LPS group rats was recovered in the LSP + CORM group, confirming the protective role of CO against sepsis-induced myocardial depression. Proteomic as well as immunoblot analysis showed that the levels of myosin heavy and light chains (MHC and MLC) as well as α-cardiac actin (ACTC) were decreased in the LPS group, and these decreases were mitigated in the LSP + CORM group, suggesting that the amounts of major contractile proteins are decreased in depressed myocardium. Not only LPS-induced inflammatory cytokine (TNFα and IL-1ß) production but also the decrease in myofilament proteins was mitigated by CORM. These results confirm the protective action of exogenously administered CO against myocardial depression during sepsis, and reveal a novel mechanism underling cardiac dysfunction during sepsis.
[Mh] Termos MeSH primário: Monóxido de Carbono/metabolismo
Proteínas Musculares/metabolismo
Miocárdio/metabolismo
Sepse/metabolismo
[Mh] Termos MeSH secundário: Actinas/genética
Actinas/metabolismo
Animais
Miosinas Cardíacas/genética
Miosinas Cardíacas/metabolismo
Cardiotônicos/farmacologia
Linhagem Celular
Citocinas/genética
Modelos Animais de Doenças
Regulação para Baixo
Expressão Gênica/efeitos dos fármacos
Lipopolissacarídeos/toxicidade
Masculino
Proteínas Musculares/genética
Contração Miocárdica/efeitos dos fármacos
Contração Miocárdica/fisiologia
Miocárdio/patologia
Compostos Organometálicos/farmacologia
Ratos
Ratos Sprague-Dawley
Proteínas Ligases SKP Culina F-Box/metabolismo
Sepse/tratamento farmacológico
Sepse/patologia
Proteínas com Motivo Tripartido/metabolismo
Ubiquitina-Proteína Ligases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Actins); 0 (Cardiotonic Agents); 0 (Cytokines); 0 (Lipopolysaccharides); 0 (Muscle Proteins); 0 (Organometallic Compounds); 0 (Tripartite Motif Proteins); 0 (tricarbonylchloro(glycinato)ruthenium(II)); 7U1EE4V452 (Carbon Monoxide); EC 2.3.2.27 (Fbxo32 protein, rat); EC 2.3.2.27 (SKP Cullin F-Box Protein Ligases); EC 2.3.2.27 (Trim63 protein, rat); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 3.6.1.- (Cardiac Myosins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171209
[St] Status:MEDLINE


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[PMID]:28467684
[Au] Autor:Wang L; Kazmierczak K; Yuan CC; Yadav S; Kawai M; Szczesna-Cordary D
[Ad] Endereço:Departments of Anatomy and Cell Biology and Internal Medicine, University of Iowa, IA, USA.
[Ti] Título:Cardiac contractility, motor function, and cross-bridge kinetics in N47K-RLC mutant mice.
[So] Source:FEBS J;284(12):1897-1913, 2017 06.
[Is] ISSN:1742-4658
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:We have investigated the physiology and mechanical profiles of skinned papillary muscle fibers from transgenic mice expressing the N47K mutation in the myosin regulatory light chain (RLC), shown to cause hypertrophic cardiomyopathy in humans. The results were compared with wild-type (WT) mice, both expressing the human ventricular RLC. Rate constants of a cross-bridge (XB) cycle were deduced from tension transients induced by sinusoidal length changes during maximal Ca activation, and were studied as a function of MgATP, MgADP, and Pi concentrations. N47K mutant showed slower XB cycles but higher actin-activated ATPase activity compared with WT. Consequently, N47K exhibited larger tension than WT. K (ADP association constant) and K (equilibrium constant of force generation) were larger in N47K, and K (ATP association constant) was slightly larger in N47K vs. WT, demonstrating stronger nucleotide binding and force generation abilities of the mutant, but no changes in rigor acto-myosin binding were observed. Tension per XB was similar among groups, but N47K exhibited more XB distribution in the attached state. Larger values of tension and higher ATPase in N47K suggested that more cross-bridges participated in tension production in the mutant myocardium compared with WT. In vivo analysis of heart function, performed in ~ 12.5-month-old mice by echocardiography and invasive hemodynamics, demonstrated a significant decrease in dP/dt -end-diastolic volume relationship, indicating a depression of ventricular contractility in N47K mice. Our findings suggest that the N47K mutation exerts its action through direct alterations of myosin motor function that ultimately result in pathological hypertrophic remodeling in N47K hearts.
[Mh] Termos MeSH primário: Atividade Motora/fisiologia
Mutação
Contração Miocárdica/fisiologia
Cadeias Leves de Miosina/genética
Músculos Papilares/fisiopatologia
[Mh] Termos MeSH secundário: Actinas/metabolismo
Difosfato de Adenosina/metabolismo
Trifosfato de Adenosina/metabolismo
Animais
Cálcio/metabolismo
Seres Humanos
Cinética
Camundongos
Camundongos Transgênicos
Cadeias Leves de Miosina/metabolismo
Miosinas
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Actins); 0 (Myosin Light Chains); 61D2G4IYVH (Adenosine Diphosphate); 8L70Q75FXE (Adenosine Triphosphate); EC 3.6.4.1 (Myosins); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1111/febs.14096


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[PMID]:29205991
[Au] Autor:Kylmälä M
[Ti] Título:Cardiac deformation imaging.
[So] Source:Duodecim;133(5):456-64, 2017.
[Is] ISSN:0012-7183
[Cp] País de publicação:Finland
[La] Idioma:eng
[Ab] Resumo:Deformation imaging (strain imaging) is an echocardiographic method for evaluating myocardial function that is also suitable for clinical use. There are two deformation imaging techniques: Tissue Doppler and 2D strain (speckle tracking). Deformation imaging allows the measurement of regional myocardial deformation in three dimensions. Longitudinal deformation (strain) measures longitudinal myocardial fiber contraction, and reflects subendocardial myocardial function, which is usually the first to deteriorate in patients with heart disease. Reduced longitudinal strain can reveal heart disease even when ejection fraction and cardiac contractility appear normal. Deformation imaging can be used for diagnosing ischemia, distinguishing between pathological and physiological hypertrophy, and early detection of heart disease in hypertension or diabetes. Global longitudinal strain (GLS) is an indicator of overall left ventricular systolic function, and correlates with the prognosis better than ejection fraction.
[Mh] Termos MeSH primário: Ecocardiografia/métodos
Cardiopatias/diagnóstico por imagem
[Mh] Termos MeSH secundário: Ecocardiografia Doppler
Testes de Função Cardíaca
Seres Humanos
Contração Miocárdica
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171206
[St] Status:MEDLINE


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[PMID]:28455633
[Au] Autor:Li L; Zhang PY; Ran H; Dong J; Fang LL; Ding QS
[Ad] Endereço:Department of Echocardiography, Nanjing First Hospital Affiliated to Nanjing Medical University, 68 Changle Road, Nanjing, Jiangsu, China.
[Ti] Título:Evaluation of left ventricular myocardial mechanics by three-dimensional speckle tracking echocardiography in the patients with different graded coronary artery stenosis.
[So] Source:Int J Cardiovasc Imaging;33(10):1513-1520, 2017 Oct.
[Is] ISSN:1875-8312
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:To investigate the relationship between left ventricular (LV) myocardial mechanics evaluated by three-dimensional speckle tracking echocardiography (3D-STE) and degree of coronary artery stenosis in patients with coronary artery disease (CAD). Ninety-seven suspected CAD patients without LV regional wall motion abnormality (RWMA) observed visually form traditional echocardiography were divided into four groups according to coronary artery angiography (CAG): 23 patients in slight stenosis group [stenosis rate (SR) ≤25%], 26 patients in mild stenosis group (25< SR ≤50%), 28 patients in moderate stenosis group (50< SR ≤75%), and 20 patients in severe stenosis group (SR >75%). Global longitudinal strain (GLS), circumferential strain (GCS), radial strain (GRS), area strain (AS) and three dimensional strain (3D-Strain) were obtained. The parameters from 3D-STE were compared between different groups and then the diagnostic value of global strains indicating different graded coronary artery stenosis was analyzed by the receiver operating characteristic curve. (1) There were significant difference in GLS, GCS, GRS, GAS and 3D-Strain between the severe stenosis group and any other group while all 3D-STE parameters except GCS in the moderate stenosis group were remarkably different from those respectively in mild group. (2) Receiver operator characteristic curve (ROC) analysis showed that the area under the curve of GLS, GRS, GCS, GAS, 3D-Strain were 0.899, 0.873, 0.723, 0.856 and 0.863 respectively for the identification of stenosis rate >50%, and 0.896, 0.866, 0.797, 0.909 and 0.899 respectively for the identification of severe stenosis. GAS less than -29.13% allowed a sensitivity of 95% and a specificity of 71.4%, while 3D strain less than 41.35% allowed a sensitivity of 90% and a specificity of 80.5% for evaluating serve coronary artery stenosis. The myocardial mechanics from 3D-STE in the CAD patients were characteristic. It could be expected to identify serve coronary stenosis with a good sensitivity and an acceptable specificity by using GAS or 3D-strain especially in the suspected CAD patients without RWMA on conventional echocardiography.
[Mh] Termos MeSH primário: Doença da Artéria Coronariana/diagnóstico por imagem
Estenose Coronária/diagnóstico por imagem
Ecocardiografia Tridimensional/métodos
Ventrículos do Coração/diagnóstico por imagem
Contração Miocárdica
Função Ventricular Esquerda
[Mh] Termos MeSH secundário: Área Sob a Curva
Fenômenos Biomecânicos
Angiografia Coronária
Doença da Artéria Coronariana/fisiopatologia
Estenose Coronária/fisiopatologia
Feminino
Ventrículos do Coração/fisiopatologia
Seres Humanos
Interpretação de Imagem Assistida por Computador
Masculino
Meia-Idade
Variações Dependentes do Observador
Valor Preditivo dos Testes
Curva ROC
Reprodutibilidade dos Testes
Índice de Gravidade de Doença
Estresse Mecânico
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.1007/s10554-017-1147-6


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[PMID]:28459744
[Au] Autor:Mohamed MA; Islas JF; Schwartz RJ; Birla RK
[Ad] Endereço:From the *Department of Biomedical Engineering, University of Houston, Houston, Texas; †Texas Heart Institute, Texas Medical Center, Houston, Texas; and ‡Department of Biology and Biochemistry, University of Houston, Houston, Texas.
[Ti] Título:Electrical Stimulation of Artificial Heart Muscle: A Look Into the Electrophysiologic and Genetic Implications.
[So] Source:ASAIO J;63(3):333-341, 2017 May/Jun.
[Is] ISSN:1538-943X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Development of tissue-engineered hearts for treatment of myocardial infarction or biologic pacemakers has been hindered by the production of mostly arrhythmic or in-synergistic constructs. Electrical stimulation (ES) of these constructs has been shown to produce tissues with greater twitch force and better adrenergic response. To further our understanding of the mechanisms underlying the effect of ES, we fabricated a bioreactor capable of delivering continuous or intermittent waveforms of various types to multiple constructs simultaneously. In this study, we examined the effect of an intermittent biphasic square wave on our artificial heart muscle (AHM) composed of neonatal rat cardiac cells and fibrin gel. Twitch forces, spontaneous contraction rates, biopotentials, gene expression profiles, and histologic observations were examined for the ES protocol over a 12 day culture period. We demonstrate improved consistency between samples for twitch force and contraction rate, and higher normalized twitch force amplitudes for electrically stimulated AHMs. Improvements in electrophysiology within the AHM were noted by higher conduction velocities and lower latency in electrical response for electrically stimulated AHMs. Genes expressing key electrophysiologic and structural markers peaked at days 6 and 8 of culture, only a few days after the initiation of ES. These results may be used for optimization strategies to establish protocols for producing AHMs capable of replacing damaged heart tissue in either a contractile or electrophysiologic capacity. Optimized AHMs can lead to alternative treatments to heart failure and alleviate the limited donor supply crisis.
[Mh] Termos MeSH primário: Coração Artificial
Miócitos Cardíacos/citologia
[Mh] Termos MeSH secundário: Animais
Reatores Biológicos
Estimulação Elétrica
Expressão Gênica
Insuficiência Cardíaca/terapia
Contração Miocárdica
Miócitos Cardíacos/fisiologia
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180104
[Lr] Data última revisão:
180104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1097/MAT.0000000000000486


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[PMID]:29206857
[Au] Autor:van Eldik W; den Adel B; Monshouwer-Kloots J; Salvatori D; Maas S; van der Made I; Creemers EE; Frank D; Frey N; Boontje N; van der Velden J; Steendijk P; Mummery C; Passier R; Beqqali A
[Ad] Endereço:Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
[Ti] Título:Z-disc protein CHAPb induces cardiomyopathy and contractile dysfunction in the postnatal heart.
[So] Source:PLoS One;12(12):e0189139, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:AIMS: The Z-disc is a crucial structure of the sarcomere and is implicated in mechanosensation/transduction. Dysregulation of Z-disc proteins often result in cardiomyopathy. We have previously shown that the Z-disc protein Cytoskeletal Heart-enriched Actin-associated Protein (CHAP) is essential for cardiac and skeletal muscle development. Furthermore, the CHAP gene has been associated with atrial fibrillation in humans. Here, we studied the misregulated expression of CHAP isoforms in heart disease. METHODS AND RESULTS: Mice that underwent transverse aortic constriction and calcineurin transgenic (Tg) mice, both models of experimental heart failure, displayed a significant increase in cardiac expression of fetal isoform CHAPb. To investigate whether increased expression of CHAPb postnatally is sufficient to induce cardiomyopathy, we generated CHAPb Tg mice under the control of the cardiac-specific αMHC promoter. CHAPb Tg mice displayed cardiac hypertrophy, interstitial fibrosis and enlargement of the left atrium at three months, which was more pronounced at the age of six months. Hypertrophy and fibrosis were confirmed by evidence of activation of the hypertrophic gene program (Nppa, Nppb, Myh7) and increased collagen expression, respectively. Connexin40 and 43 were downregulated in the left atrium, which was associated with delayed atrioventricular conduction. Tg hearts displayed both systolic and diastolic dysfunction partly caused by impaired sarcomere function evident from a reduced force generating capacity of single cardiomyocytes. This co-incided with activation of the actin signalling pathway leading to the formation of stress fibers. CONCLUSION: This study demonstrated that the fetal isoform CHAPb initiates progression towards cardiac hypertrophy, which is accompanied by delayed atrioventricular conduction and diastolic dysfunction. Moreover, CHAP may be a novel therapeutic target or candidate gene for screening in cardiomyopathies and atrial fibrillation.
[Mh] Termos MeSH primário: Cardiomiopatias/metabolismo
Proteínas dos Microfilamentos/metabolismo
Proteínas Musculares/metabolismo
Contração Miocárdica
Isoformas de Proteínas/metabolismo
[Mh] Termos MeSH secundário: Animais
Camundongos
Camundongos Transgênicos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Microfilament Proteins); 0 (Muscle Proteins); 0 (Protein Isoforms); 0 (Synpo2l protein, mouse)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171229
[Lr] Data última revisão:
171229
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171206
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189139



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