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1.
Toxicol Lett ; 318: 1-11, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31618665

RESUMO

Triptolide (TP), a principal bioactive component extracted from traditional Chinese medicine Tripterygium wilfordii Hook. F. (TWHF), has attracted wide attention of its therapeutic effects on inflammation and autoimmune diseases. However, the therapeutic application of TP is hindered by severe cardiomyocyte toxicity and narrow therapeutic window. We previously identified that the p53 was an indispensable contributor in TP-induced myocardial injury. p53 has an inhibitory effect on IKKß-NF-κB pathway that regulates glucose transporters (GLUT) expression. Based on these evidences, we speculate that p53 mediates TP-disturbed glucose uptake by blocking IKKß-NF-κB signaling. This study focused on the effect of TP on cardiac glucose uptake and the role of p53 in glucose metabolism in cardiomyocytes, and p53 -/- mice. TP treatment depressed glucose consumption and ATP production resulting in myocardial damage. Incubation with ATP (5 mM) remarkably decreased the cellular damage. Immunoblotting and immunofluorescence identified that TP suppressed glucose uptake by restricting IKKß-NF-κB signaling activation, GLUT1 and GLUT4 expression. p53 inhibition alleviated the cell damage and the compromise of glucose uptake. Mechanistically, p53 antagonist PFTα abolished TP-induced the inhibition of IKKß, IκBα phosphorylation, p65 nuclear translocation, and GLUT1, GLUT4 expression. Consistently, in acute heart injury models, p53 deficiency upregulated IKKß-NF-κB activation and GLUT1, GLUT4 protein levels which was also indicated as amelioration of heart histological injury after 1.2 mg kg-1 TP administration. The present findings indicate that TP-induced p53 overactivation suppresses glucose uptake by inhibiting IKKß-NF-κB pathway and downregulating NF-κB-dependent GLUT1 and GLUT4 expression.


Assuntos
Diterpenos/toxicidade , Glucose/metabolismo , Cardiopatias/induzido quimicamente , Quinase I-kappa B/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , NF-kappa B/metabolismo , Fenantrenos/toxicidade , Proteína Supressora de Tumor p53/metabolismo , Animais , Apoptose/efeitos dos fármacos , Cardiotoxicidade , Linhagem Celular , Metabolismo Energético/efeitos dos fármacos , Compostos de Epóxi/toxicidade , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Cardiopatias/genética , Cardiopatias/metabolismo , Cardiopatias/patologia , Camundongos Knockout , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/deficiência , Proteína Supressora de Tumor p53/genética
3.
Medicine (Baltimore) ; 98(38): e17256, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567998

RESUMO

RATIONALE: Cardiac amyloidosis, considered for the last years to be a rare disease, is one of the determinants of HFpEF. The non-specific clinical presentation and the difficulties related to endomyocardial biopsy have made cardiac amyloidosis an underdiagnosed clinical entity. Improvement of non-invasive diagnostic techniques and the development of new therapies increased clinical awareness for this form of restrictive cardiomyopathy. We here summarize echocardiography and Tc-HDP scintigraphy findings in 6 cases of cardiac amyloidosis and review the literature data of this progressive and fatal cardiomyopathy. PATIENTS CONCERNS: The main clinical manifestations were fatigue, low exercise tolerance and edemas. The right heart failure symptoms usually dominated the clinical picture. DIAGNOSES: All cases were evaluated by echocardiography; 3 cases were further examined by bone scintigraphy and 4 cases a peripheral biopsy was performed. Electrocardiography showed low-voltage QRS complexes and "pseudo-infarct" pattern in the precordial leads, contrary to the echocardiographic aspect, which revealed thickening of ventricle walls. Biatrial dilation and diastolic disfunction were observed. Impaired systolic function was detected in advanced stages of the disease. Tc-HDP scintigraphy revealed cardiac uptake of radiopharmaceutical and managed to confirm the diagnosis in 1 case of cardiac amyloidosis in which salivary gland biopsy was negative. INTERVENTIONS: The treatment was based on managing fluid balance, with the mainstream therapy represented by diuretics. Neurohormonal agents, usually used in heart failure treatment were avoided, due to poor tolerance and worsening of disease course. The management of these 6 cases was challenging due to the refractory manifestation of congestive heart failure. OUTCOMES: During follow-up, 4 of the 6 patients from the current study died in the first year after the final diagnosis was established. LESSONS: Nuclear imaging of cardiac amyloidosis has a revolutionary development nowadays. Bone scintigraphy presents promising results for identifying patients at early stages of disease and to differentiate between cardiac amyloidosis types. Further studies are necessary for the standardization of imaging protocol and development of non-invasive diagnostic tools, especially in assessing the response to treatment and disease progression, for which little is known.


Assuntos
Amiloidose/diagnóstico por imagem , Ecocardiografia , Cardiopatias/diagnóstico por imagem , Cintilografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Amiloidose/diagnóstico , Amiloidose/patologia , Difosfonatos , Feminino , Coração/diagnóstico por imagem , Cardiopatias/diagnóstico , Cardiopatias/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Compostos de Organotecnécio
5.
Scand Cardiovasc J ; 53(6): 329-336, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31455109

RESUMO

Objectives. Although deuterium oxide (D2O) has preservative property on the extracted organ, whether D2O also protects the in situ myocardial injury remains unknown. Using cardiac microdialysis, local administration of D2O through dialysis probe was applied in situ rat heart. We examined the effect of the D2O on the myocardial injury induced ischemia, reperfusion, and chemical hypoxia. Methodology. We measured dialysate myoglobin levels during 30 min of coronary occlusion and reperfusion in the absence and presence of D2O. Furthermore, to confirm the effect of D2O on NaCN induced myocardial injury, we measured the dialysate myoglobin levels with local perfusion of NaCN in the absence and presence of D2O. Results. The dialysate myoglobin levels increased from 177 ± 45 ng/mL at baseline to 3030 ± 1523 ng/mL during 15-30 min of coronary occlusion and further increased to 8588 ± 1684ng/mL at 0-15 min of reperfusion. The dialysate myoglobin levels with 60 min local perfusion of NaCN increased to 1214 ± 279 ng/mL. D2O attenuated myocardial myoglobin release during 15-30 min of coronary occlusion and 0-30 min of reperfusion and 15-60 min of local perfusion of NaCN. Conclusions. D2O might have a beneficial effect of myocardium against ischemia, reperfusion and chemical hypoxia.


Assuntos
Óxido de Deutério/farmacologia , Cardiopatias/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/patologia , Animais , Modelos Animais de Doenças , Cardiopatias/induzido quimicamente , Cardiopatias/metabolismo , Cardiopatias/patologia , Masculino , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/metabolismo , Mioglobina/metabolismo , Ratos Sprague-Dawley , Cianeto de Sódio , Fatores de Tempo
6.
Medicine (Baltimore) ; 98(31): e16640, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374034

RESUMO

RATIONALE: Tumors in the heart are rare. Myxomas, rhabdomyomas, and fibromas are the most common benign cardiac tumors. Hamartoma of mature cardiomyocytes (HMCM) is another benign cardiac tumor, are very rare and have only been reported in a few literatures. PATIENT CONCERNS: We report a case of 41-year-old male who suffered short of breath for 3 years, and lower limbs edema for 2 years. DIAGNOSES: Transthoracic echocardiogram (TTE) and cardiac magnetic resonance (CMR) showed a large amount of pericardial effusion and confirmed a mass of 18 × 14 mm on the superior vena cava near the outer edge of right atrium. The patient was first diagnosed as pleural mesothelioma. Surgery was performed to relieve the symptoms and confirm diagnoses. However, during surgery, we found the right atrium is apparently thicken with rough and uneven surface. Histology of right atrium mass indicated it as hamartoma of mature cardiomyocytes. INTERVENTION: We resected the thicken atrial wall completely, reconstructed right atrium with bovine pericardial patch, and resected the pericardium. OUTCOMES: Patient was discharged 9 days after surgery, and remained asymptomatic during 9 months follow up. LESSONS: Hamartoma of mature cardomyocytes is a rare benign cardiac tumor. There were 26 cases reported until now. The conclusive diagnosis depends on pathological sections. For patients with symptoms, surgery is an effective treatment for HMCM.


Assuntos
Hamartoma/patologia , Átrios do Coração/patologia , Cardiopatias/patologia , Miócitos Cardíacos/patologia , Adulto , Dispneia/etiologia , Ecocardiografia , Edema/etiologia , Hamartoma/complicações , Hamartoma/cirurgia , Cardiopatias/complicações , Cardiopatias/cirurgia , Humanos , Masculino
7.
Physiol Rev ; 99(4): 1765-1817, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31364924

RESUMO

Twelve regulated cell death programs have been described. We review in detail the basic biology of nine including death receptor-mediated apoptosis, death receptor-mediated necrosis (necroptosis), mitochondrial-mediated apoptosis, mitochondrial-mediated necrosis, autophagy-dependent cell death, ferroptosis, pyroptosis, parthanatos, and immunogenic cell death. This is followed by a dissection of the roles of these cell death programs in the major cardiac syndromes: myocardial infarction and heart failure. The most important conclusion relevant to heart disease is that regulated forms of cardiomyocyte death play important roles in both myocardial infarction with reperfusion (ischemia/reperfusion) and heart failure. While a role for apoptosis in ischemia/reperfusion cannot be excluded, regulated forms of necrosis, through both death receptor and mitochondrial pathways, are critical. Ferroptosis and parthanatos are also likely important in ischemia/reperfusion, although it is unclear if these entities are functioning as independent death programs or as amplification mechanisms for necrotic cell death. Pyroptosis may also contribute to ischemia/reperfusion injury, but potentially through effects in non-cardiomyocytes. Cardiomyocyte loss through apoptosis and necrosis is also an important component in the pathogenesis of heart failure and is mediated by both death receptor and mitochondrial signaling. Roles for immunogenic cell death in cardiac disease remain to be defined but merit study in this era of immune checkpoint cancer therapy. Biology-based approaches to inhibit cell death in the various cardiac syndromes are also discussed.


Assuntos
Morte Celular , Citotoxicidade Imunológica , Cardiopatias/patologia , Mitocôndrias Cardíacas/patologia , Miocárdio/patologia , Animais , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Autofagia , Proteínas Relacionadas à Autofagia/metabolismo , Cardiopatias/imunologia , Cardiopatias/metabolismo , Cardiopatias/fisiopatologia , Humanos , Mitocôndrias Cardíacas/imunologia , Mitocôndrias Cardíacas/metabolismo , Miocárdio/imunologia , Miocárdio/metabolismo , Necrose , Piroptose , Transdução de Sinais
8.
Cardiovasc Pathol ; 42: 59-63, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31351216

RESUMO

This article reviews the surgical considerations of cardiac allograft rejection after heart transplantation and describes current treatment modalities for the failing graft. Cardiac allograft rejection can be a moribund diagnosis, especially when it is acute and high grade. It is broadly categorized into hyperacute, acute cellular, and antibody-mediated rejection. Treatment includes a multitude of medical and immunomodulation therapies for graft recovery. Severe rejection requires mechanical circulatory support for hemodynamic stability to maintain end-organ function. Retransplantation for graft loss is the ultimate therapy; however, it portends poor outcomes.


Assuntos
Oxigenação por Membrana Extracorpórea , Rejeição de Enxerto/terapia , Sobrevivência de Enxerto/efeitos dos fármacos , Cardiopatias/terapia , Transplante de Coração/efeitos adversos , Coração Auxiliar , Imunossupressores/uso terapêutico , Oxigenação por Membrana Extracorpórea/efeitos adversos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Rejeição de Enxerto/fisiopatologia , Cardiopatias/etiologia , Cardiopatias/patologia , Cardiopatias/fisiopatologia , Humanos , Imunossupressores/efeitos adversos , Recuperação de Função Fisiológica , Reoperação , Fatores de Risco , Resultado do Tratamento
11.
Nat Commun ; 10(1): 3111, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31308376

RESUMO

Biomedical repositories such as the UK Biobank provide increasing access to prospectively collected cardiac imaging, however these data are unlabeled, which creates barriers to their use in supervised machine learning. We develop a weakly supervised deep learning model for classification of aortic valve malformations using up to 4,000 unlabeled cardiac MRI sequences. Instead of requiring highly curated training data, weak supervision relies on noisy heuristics defined by domain experts to programmatically generate large-scale, imperfect training labels. For aortic valve classification, models trained with imperfect labels substantially outperform a supervised model trained on hand-labeled MRIs. In an orthogonal validation experiment using health outcomes data, our model identifies individuals with a 1.8-fold increase in risk of a major adverse cardiac event. This work formalizes a deep learning baseline for aortic valve classification and outlines a general strategy for using weak supervision to train machine learning models using unlabeled medical images at scale.


Assuntos
Valva Aórtica/anormalidades , Doenças das Valvas Cardíacas/patologia , Aprendizado de Máquina , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/patologia , Cardiopatias/patologia , Doenças das Valvas Cardíacas/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Aprendizado de Máquina Supervisionado
12.
Magn Reson Imaging Clin N Am ; 27(3): 563-574, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31279457

RESUMO

Cardiac fibrosis, characterized by net accumulation of extracellular matrix in the myocardium, is a common final pathway of heart failure. This myocardial fibrosis (MF) is not necessarily the primary cause of dysfunction; it often results from a reparative process activated in response to cardiomyocyte injury. In light of currently available treatments, late-identified MF could be definitive or irreversible, associated with worsening ventricular systolic function, abnormal cardiac remodeling, and increased ventricular stiffness and arrhythmia. T1 mapping should be used to detect incipient changes leading to myocardial damage in several clinical conditions and also in subclinical disease. This article reviews available techniques for MF detection, focusing on noninvasive quantification of diffuse fibrosis and clinical applications.


Assuntos
Cardiopatias/diagnóstico por imagem , Cardiopatias/patologia , Imagem por Ressonância Magnética/métodos , Fibrose , Coração/diagnóstico por imagem , Humanos , Miocárdio/patologia
13.
J Korean Acad Nurs ; 49(3): 329-339, 2019 Jun.
Artigo em Coreano | MEDLINE | ID: mdl-31266929

RESUMO

PURPOSE: The purpose of this study was to investigate the frequency, patterns, and factors of reversals in decisions about life-sustaining treatment (LST) among older patients with terminal-stage chronic cardiopulmonary disease. METHODS: This was a retrospective correlational descriptive study based on medical chart review. De-identified patient electronic medical record data were collected from 124 deceased older patients with terminal-stage cardiopulmonary disease who had made reversals of LST decisions in an academic tertiary hospital in 2015. Data were extracted about the reversed LST decisions, LST treatments applied before death, and patients' demographic and clinical factors. Multivariate logistic regression analysis was used to identify the factors associated with the reversal to higher intensity of LST treatment. RESULTS: The use of inotropic agents was the most frequently reversed LST treatment, followed by cardiopulmonary resuscitation, intubation, ventilator therapy, and hemodialysis. Inconsistency between the last LST decisions and actual treatments occurred most often in hemodialysis. One-third of the reversals in LST decisions were made toward higher intensity of LST treatment. Patients who had lung diseases (vs. heart diseases); were single, divorced, or bereaved (vs. married); and had an acquaintance as a primary decision maker (vs. the patients themselves) were significantly more likely to reverse the LST decisions to higher intensity of LST treatment. CONCLUSION: This study demonstrated the complex and turmoil situation of the LST decision-making process among older patients with terminal-stage cardiopulmonary disease and suggests the importance of support for patients and families in their LST decision-making process.


Assuntos
Tomada de Decisões , Cardiopatias/patologia , Pneumopatias/patologia , Idoso , Idoso de 80 Anos ou mais , Reanimação Cardiopulmonar , Doença Crônica , Feminino , Cardiopatias/terapia , Humanos , Pneumopatias/terapia , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Assistência Terminal
14.
J Zoo Wildl Med ; 50(2): 482-486, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31260220

RESUMO

A 0.5 kg, 5-yr-old male bearded dragon (Pogona vitticeps) presented with a 2-mo history of lethargy, anorexia, and impaired locomotion. Upon physical examination, bradyarrhythmia (heart rate: 20 beats/min) and balance disorders were noted. Electrocardiography revealed a first-degree atrioventricular block (P-R interval: 360 ms). On echocardiography, all cardiac chambers were slightly above normal ranges. Complete blood count, blood biochemistry, and T4 were unremarkable except for mildly elevated aspartate aminotransferase. Adenovirus testing was negative by polymerase chain reaction. Following euthanasia, necropsy revealed marked thickening of the arterial trunks and histopathology confirmed multifocal atherosclerosis of efferent heart vessels, arteriosclerosis of cerebral arterioles, and multifocal spongiosis of brain tissue, more pronounced in the optic chiasma. Owing to its severity, atherosclerosis may have contributed to chronic arterial hypertension with damages to the heart, brain vessels, and brain tissue-optic chiasma.


Assuntos
Aterosclerose/veterinária , Bloqueio Atrioventricular/veterinária , Encefalopatias/veterinária , Cardiopatias/veterinária , Hipertensão/veterinária , Lagartos , Animais , Aterosclerose/patologia , Bloqueio Atrioventricular/patologia , Encefalopatias/etiologia , Encefalopatias/patologia , Cardiopatias/etiologia , Cardiopatias/patologia , Hipertensão/complicações , Masculino
15.
Neuropeptides ; 76: 101941, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31256921

RESUMO

Substance P (SP) is an undecapeptide encoding the tachykinin 1 (TAC1) gene and belongs to the tachykinin family. SP is widely distributed in the central nervous system and the peripheral nervous system. SP is also produced by nonneuronal cells, such as inflammatory cells and endothelial cells. The biological activities of SP are mainly regulated through the high-affinity neurokinin 1 receptor (NK-1R). The SP/NK-1R system plays an important role in the molecular bases of many human pathophysiologic processes, such as pain, infectious and inflammatory diseases, and cancer. In addition, this system has been implicated in fibrotic diseases and processes such as wound healing, myocardial fibrosis, bowel fibrosis, myelofibrosis, renal fibrosis, and lung fibrosis. Recently, studies have shown that SP plays an important role in liver fibrosis and that NK-1R antagonists can inhibit the progression of fibrosis. NK-1R receptor antagonists could provide clinical solutions for fibrotic diseases. This review summarizes the structure and function of SP and its involvement in fibrotic diseases.


Assuntos
Fibrose/metabolismo , Substância P/metabolismo , Animais , Doenças da Córnea/metabolismo , Doenças da Córnea/patologia , Cardiopatias/metabolismo , Cardiopatias/patologia , Humanos , Inflamação/metabolismo , Artropatias/metabolismo , Artropatias/patologia , Nefropatias/metabolismo , Nefropatias/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Mielofibrose Primária/metabolismo , Mielofibrose Primária/patologia , Cicatrização
17.
Virchows Arch ; 475(3): 335-340, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31254069

RESUMO

Pulmonary dirofilariasis is an infection caused by Dirofilaria immitis, which is an endemic parasite in Japan. We experienced 13 surgical cases of pulmonary dirofilariasis in our hospital. Of the 13 patients, 61.5% were men. The responsible lesions were located in the right lung in all cases, and 76.9% of them were in the lower lobe. Histologically, 12 cases showed necrotic nodules with peripheral granuloma with worms inside the pulmonary artery. One case did not show a necrotic nodule but showed only thickening and hyalinization of the pulmonary artery wall with a degenerated worm inside. Eosinophils were found histologically in all cases. Thirteen cases of dirofilariasis in one institution seem to be the largest number in Japan, based on previous reports. One reason for this increased prevalence may be the hot and humid climate of our prefecture considering the ecology of the mosquito as a vector. Elastic staining and eosinophils in peripheral granulomatous areas can contribute to the diagnosis when the worms are degenerated.


Assuntos
Dirofilariose/diagnóstico , Dirofilariose/patologia , Pneumopatias/metabolismo , Adulto , Idoso , Animais , Diagnóstico Diferencial , Dirofilaria immitis/patogenicidade , Dirofilariose/etiologia , Eosinófilos/patologia , Feminino , Cardiopatias/patologia , Humanos , Japão , Pulmão/patologia , Pneumopatias/etiologia , Pneumopatias Parasitárias/patologia , Masculino , Pessoa de Meia-Idade
18.
Cardiovasc Pathol ; 42: 6-9, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31158730

RESUMO

Intracapillary lipoprotein thrombi are a distinct histopathologic finding described in the setting of lipoprotein glomerulopathy. The disease is associated with mutations in the apolipoprotein E gene and responds well to lipid-lowering treatments. Lipoprotein glomerulopathy is thought to primarily affect the kidneys, and lipoprotein thrombi have never been described in any other organ. Herein we present the first recognized case with extrarenal manifestations in the form of intravascular cardiac lipoprotein deposition.


Assuntos
Vasos Coronários/ultraestrutura , Cardiopatias/patologia , Nefropatias/patologia , Proteinose Lipoide de Urbach e Wiethe/patologia , Apolipoproteína E3/genética , Apolipoproteínas E/genética , Predisposição Genética para Doença , Cardiopatias/genética , Humanos , Nefropatias/genética , Proteinose Lipoide de Urbach e Wiethe/genética , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo
19.
Int J Mol Med ; 44(2): 417-426, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173172

RESUMO

Myocardial injury is one of the main symptoms of sepsis. However, the mechanisms underlying sepsis­induced myocardial dysfunction remain unclear. In the present study, the concentration of cardiac troponin T (CTnT) in serum was measured using an enzyme­linked immunosorbent assay kit. The levels of interleukin (IL)­1ß and IL­18 were assessed by reverse transcription­quantitative polymerase chain reaction (RT­qPCR) analysis and the level of malondialdehyde (MDA) was determined using a corresponding kit. Myocardial pathology was analyzed via hematoxylin and eosin staining. RT­qPCR analysis and western blotting and/or immunohistochemistry were used to quantify the expression levels of thioredoxin­interacting protein (TNXIP), NOD­like receptor pyrin domain containing 3 (NLRP3), cleaved caspase­1, caspase­1, catalase and manganese­superoxide dismutase (MnSOD). The viability of cells was determined using a cell counting kit­8. Apoptosis and reactive oxygen species (ROS) were examined using flow cytometry. Models of sepsis­induced myocardial injury were successfully established; evidence included increases in the levels of CTnT, IL­1ß, IL­18 and MDA and myocardial tissue damage in vivo, and decreased cell viability and improvements in IL­1ß and IL­18 in vitro. The levels of TXNIP, NLRP3 and cleaved caspase­1 were upregulated in the sepsis models. Small interfering RNA targeting TNXNIP (siTXNIP) increased cell viability, reduced the apoptotic rate and attenuated the release of IL­1ß and IL­18. The levels of TXNIP, NLRP3 and cleaved caspase­1 and production of ROS were suppressed by siTXNIP, accompanied by increases in catalase and MnSOD. TXNIP/NLRP3 serves an important role in the development of sepsis­induced myocardial damage.


Assuntos
Proteínas de Ciclo Celular/análise , Cardiopatias/etiologia , Miocárdio/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/análise , Sepse/complicações , Animais , Apoptose , Linhagem Celular , Cardiopatias/patologia , Masculino , Ratos Sprague-Dawley , Sepse/patologia
20.
Oxid Med Cell Longev ; 2019: 4578175, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31210840

RESUMO

NADPH oxidase (Nox) is considered a major source of reactive oxygen species (ROS) in the heart in normal and pathological conditions. However, the role of Nox in severe acute pancreatitis- (SAP-) associated cardiac injury remains unclear. Therefore, we aim to investigate the contribution of Nox to SAP-associated cardiac injury and to explore the underlying molecular mechanisms. Apocynin, a Nox inhibitor, was given at 20 mg/kg for 30 min before SAP induction by a retrograde pancreatic duct injection of 5% sodium taurocholate. Histopathological staining, Nox activity and protein expression, oxidative stress markers, apoptosis and associated proteins, cardiac-related enzyme indexes, and cardiac function were assessed in the myocardium in SAP rats. The redox-sensitive MAPK signaling molecules were also examined by western blotting. SAP rats exhibited significant cardiac impairment along with increased Nox activity and protein expression, ROS production, cell apoptosis, and proapoptotic Bax and cleaved caspase-3 protein levels. Notably, Nox inhibition with apocynin prevented SAP-associated cardiac injury evidenced by a decreased histopathologic score, cardiac-related enzymes, and cardiac function through the reduction of ROS production and cell apoptosis. This protective role was further confirmed by a simulation experiment in vitro. Moreover, we found that SAP-induced activation in MAPK signaling molecules in cardiomyocytes was significantly attenuated by Nox inhibition. Our data provide the first evidence that Nox hyperactivation acts as the main source of ROS production in the myocardium, increases oxidative stress, and promotes cell apoptosis via activating the MAPK pathway, which ultimately results in cardiac injury in SAP.


Assuntos
Apoptose , Regulação Enzimológica da Expressão Gênica , Cardiopatias/enzimologia , Miocárdio/enzimologia , NADPH Oxidases/metabolismo , Pancreatite/enzimologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Caspase 3/biossíntese , Modelos Animais de Doenças , Cardiopatias/etiologia , Cardiopatias/patologia , Sistema de Sinalização das MAP Quinases , Masculino , Miocárdio/patologia , NADPH Oxidases/antagonistas & inibidores , Pancreatite/induzido quimicamente , Pancreatite/complicações , Pancreatite/patologia , Ratos , Índice de Gravidade de Doença , Proteína X Associada a bcl-2/biossíntese
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