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1.
J Mol Histol ; 51(6): 613-628, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33011887

RESUMO

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) in December 2019 form Wuhan, China leads to coronavirus disease 2019 (COVID-19) pandemic. While the common cold symptoms are observed in mild cases, COVID-19 is accompanied by multiorgan failure in severe patients. The involvement of different organs in severe patients results in lengthening the hospitalization duration and increasing the mortality rate. In this review, we aimed to investigate the involvement of different organs in COVID-19 patients, particularly in severe cases. Also, we tried to define the potential underlying mechanisms of SARS-CoV2 induced multiorgan failure. The multi-organ dysfunction is characterized by acute lung failure, acute liver failure, acute kidney injury, cardiovascular disease, and as well as a wide spectrum of hematological abnormalities and neurological disorders. The most important mechanisms are related to the direct and indirect pathogenic features of SARS-CoV2. Although the presence of angiotensin-converting enzyme 2, a receptor of SARS-CoV2 in the lung, heart, kidney, testis, liver, lymphocytes, and nervous system was confirmed, there are controversial findings to about the observation of SARS-CoV2 RNA in these organs. Moreover, the organ failure may be induced by the cytokine storm, a result of increased levels of inflammatory mediators, endothelial dysfunction, coagulation abnormalities, and infiltration of inflammatory cells into the organs. Therefore, further investigations are needed to detect the exact mechanisms of pathogenesis. Since the involvement of several organs in COVID-19 patients is important for clinicians, increasing their knowledge may help to improve the outcomes and decrease the rate of mortality and morbidity.


Assuntos
Infecções por Coronavirus/patologia , Cardiopatias/patologia , Nefropatias/patologia , Hepatopatias/patologia , Insuficiência de Múltiplos Órgãos/patologia , Pneumonia Viral/patologia , Betacoronavirus , Síndrome da Liberação de Citocina/patologia , Cardiopatias/virologia , Humanos , Rim/patologia , Nefropatias/virologia , Fígado/patologia , Hepatopatias/virologia , Pulmão/patologia , Insuficiência de Múltiplos Órgãos/virologia , Miocárdio/patologia , Pandemias , Peptidil Dipeptidase A/metabolismo
2.
Biomed Environ Sci ; 33(8): 603-613, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32933612

RESUMO

Objective: To detect the effects of shortwave radiation on dose-dependent cardiac structure and function in rats after radiation and to elucidate the mechanism of shortwave radiation induced cardiac injury to identify sensitive indicators and prophylactic treatment. Methods: One hundred Wistar rats were either exposed to 27 MHz continuous shortwave at a power density of 5, 10, and 30 mW/cm 2 for 6 min or undergone sham exposure for the control (the rats had to be placed in the exposure system with the same schedules as the exposed animals, but with an inactive antenna). The Ca 2+, glutamic oxaloacetic transaminase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) content in the peripheral serum of the rats were detected by an automatic blood biochemical analyser. The electrocardiogram (ECG) of standard lead II was recorded by a multi-channel physiological recording and analysis system. The cardiac structure of rats was observed by light and electron microscopy. Results: The results showed that the 5, 10, and 30 mW/cm 2 shortwave radiation caused a significant increased in the levels of Ca 2+, AST, CK, and LDH in the peripheral serum of rats. The cardiac structure was damaged by radiation and showed a disordered arrangement of myocardial fibres, the cavitation and swelling of myocardial mitochondria. These injuries were most significant 7 d after radiation and were not restored until 28 d after radiation. Conclusion: Shortwave radiation of 5, 10, and 30 mW/cm 2 can damage rat cardiac function, including damage to the tissue structure and ultrastructure, especially at the level of the myocardial fibres and mitochondria. Shortwave radiation at 5, 10, and 30 mW/cm 2 induced damage to rat heart function and structure with a dose-effect relationship, i.e., the greater the radiation dose was, the more significant the damage was.


Assuntos
Cardiopatias/patologia , Coração/efeitos da radiação , Miocárdio/patologia , Ondas de Rádio/efeitos adversos , Animais , Relação Dose-Resposta à Radiação , Cardiopatias/etnologia , Cardiopatias/fisiopatologia , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar
3.
Life Sci ; 260: 118392, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32898523

RESUMO

AIMS: We aimed to investigate the impact of cancer cachexia and previous aerobic exercise training (AET) on cardiac function and structure in tumor bearing mice. MAIN METHODS: Colon adenocarcinoma cells 26 (CT26) were subcutaneously injected in BALB/c mice to establish robust cancer cachexia model. AET was performed on a treadmill during 45 days, 60 min/5 days per week. Cardiac function was evaluated by echocardiography and cardiac morphology was assessed by light microscopy. The protein expression levels of mitochondrial complex were analyzed by Western blotting. The mRNA levels of genes related to cardiac remodeling and autophagy were analyzed by quantitative Real-Time PCR. KEY FINDINGS: Our data confirms CT26 tumor bearing mice as a well-characterized and robust model of cancer cachexia. CT26 mice exhibited cardiac remodeling and dysfunction characterized by cardiac atrophy and impaired left ventricle ejection fraction paralleled by cardiac necrosis, inflammation and fibrosis. AET partially reversed the left ventricle ejection fraction and led to significant anti-cardiac remodeling effect associated reduced necrosis, inflammation and cardiac collagen deposition in CT26 mice. Reduced TGF-ß1 mRNA levels, increased mitochondrial complex IV protein levels and partial recovery of BNIP3 mRNA levels in cardiac tissue were associated with the cardiac effects of AET in CT26 mice. Thus, we suggest AET as a powerful regulator of key pathways involved in cardiac tissue homeostasis in cancer cachexia. SIGNIFICANCE: Our study provides a robust model of cancer cachexia, as well as highlights the potential and integrative effects of AET as a preventive strategy for reducing cardiac damage in cancer cachexia.


Assuntos
Caquexia/etiologia , Neoplasias do Colo/complicações , Cardiopatias/terapia , Condicionamento Físico Animal , Remodelação Ventricular , Animais , Caquexia/patologia , Neoplasias do Colo/patologia , Cardiopatias/etiologia , Cardiopatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Asian Cardiovasc Thorac Ann ; 28(8): 500-503, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32757656

RESUMO

A regular check up on a 59-year-old man showed a high carcinoembryonic antigen level in his blood. A computed tomography scan showed tumors in the right atrium. We performed tumor resection successfully. The resected specimen was found to be blood cysts that had developed from the right atrium to the inferior vena cava. Intracardiac blood cysts are generally observed in infants, spontaneously disappear during the first 6 months of life, and are located in the left side of heart and on atrioventricular valves. Therefore, this case is extremely rare. Also, it is worth considering the timing of this surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Cistos/cirurgia , Átrios do Coração/cirurgia , Cardiopatias/cirurgia , Tempo para o Tratamento , Cistos/diagnóstico por imagem , Cistos/patologia , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/patologia , Cardiopatias/diagnóstico por imagem , Cardiopatias/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
5.
Life Sci ; 260: 118315, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32835697

RESUMO

AIMS: Cardiac dysfunction is the main cause of multi-organ failure following sepsis within critical care units. The present study aimed to investigate the effects of the small molecule inhibition of cyclic GMP-AMP synthase (cGAS), RU.521, on cardiac function in mice with sepsis. MATERIALS AND METHODS: Sepsis was induced in mice via intraperitoneal lipopolysaccharide (LPS) injection (10 mg/kg, i.p.). Mice subsequently received 5 mg/kg RU.521 within 10 min form LPS injection. The cardiac function, inflammatory factor and oxidative stress of mice were examined for 24 h following LPS injection. KEY FINDINGS: RU.521 was indicated to significantly increase the cardiac function of mice with sepsis. In addition, the inflammatory responses, oxidative stress and apoptosis in hearts of sepsis mice were markedly mitigated by RU.521. Moreover, inhibition of Sirt3 inhibited the protective effects of RU.521 on mice with sepsis. SIGNIFICANCE: The current study indicated that RU.521 alleviated the inflammatory response and alleviated the damage induced by oxidative stress, leading to cardiac protection via increased Sirt3 expression in the hearts of mice with sepsis.


Assuntos
Benzofuranos/farmacologia , Cardiopatias/tratamento farmacológico , Nucleotidiltransferases/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Sepse/complicações , Animais , Apoptose , Cardiopatias/enzimologia , Cardiopatias/etiologia , Cardiopatias/patologia , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Sepse/induzido quimicamente , Sepse/patologia , Transdução de Sinais
6.
PLoS One ; 15(7): e0232507, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32645007

RESUMO

Sex-related differences in cardiovascular diseases are highly complex in humans and model-dependent in experimental laboratory animals. The objective of this work was to comprehensively investigate key sex differences in the response to acute and prolonged adrenergic stimulation in C57Bl/6NCrl mice. Cardiac function was assessed by trans-thoracic echocardiography before and after acute adrenergic stimulation (a single sub-cutaneous dose of isoproterenol 10 mg/kg) in 15 weeks old male and female C57Bl/6NCrl mice. Thereafter, prolonged adrenergic stimulation was achieved by sub-cutaneous injections of isoproterenol 10 mg/kg/day for 14 days in male and female mice. Cardiac function and morphometry were assessed by trans-thoracic echocardiography on the 15th day. Thereafter, the mice were euthanized, and the hearts were collected. Histopathological analysis of myocardial tissue was performed after staining with hematoxylin & eosin, Masson's trichrome and MAC-2 antibody. Gene expression of remodeling and fibrotic markers was assessed by real-time PCR. Cardiac function and morphometry were also measured before and after isoproterenol 10 mg/kg/day for 14 days in groups of gonadectomized male and female mice and sham-operated controls. In the current work, there were no statistically significant differences in the positive inotropic and chronotropic effects of isoproterenol between male and female C57Bl/6NCrl. After prolonged adrenergic stimulation, there was similar degree of cardiac dysfunction, cardiac hypertrophy, and myocardial fibrosis in male and female mice. Similarly, prolonged isoproterenol administration induced hypertrophic and fibrotic genes in hearts of male and female mice to the same extent. Intriguingly, gonadectomy of male and female mice did not have a significant impact on isoproterenol-induced cardiac dysfunction as compared to sham-operated animals. The current work demonstrated lack of significant sex-related differences in isoproterenol-induced cardiac hypertrophy, dysfunction, and fibrosis in C57Bl/6NCrl mice. This study suggests that female sex may not be sufficient to protect the heart in this model of isoproterenol-induced cardiac dysfunction and underscores the notion that sexual dimorphism in cardiovascular diseases is highly model-dependent.


Assuntos
Cardiopatias/fisiopatologia , Caracteres Sexuais , Animais , Biomarcadores/metabolismo , Cardiomegalia/induzido quimicamente , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Modelos Animais de Doenças , Ecocardiografia , Feminino , Cardiopatias/induzido quimicamente , Cardiopatias/metabolismo , Cardiopatias/patologia , Isoproterenol/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ovariectomia
7.
Int J Cardiovasc Imaging ; 36(11): 2249-2250, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32677022

RESUMO

CMR provides pathology-like insights of myocardial abnormality, such as hyperemia, edema, necrosis and fibrosis, which is in-vivo, non-invasive and real-time. Hence, it is most likely to become one alternative tool for mimicking pathology, so-called pathologicalized imaging due to its extraordinary tissue characteristics. This article aims to call for a wider clinical application of CMR with more attention on its tissue characterization value.


Assuntos
Cardiopatias/diagnóstico por imagem , Cardiopatias/patologia , Imagem por Ressonância Magnética , Miocárdio/patologia , Biópsia , Edema Cardíaco/diagnóstico por imagem , Edema Cardíaco/patologia , Fibrose , Humanos , Hiperemia/diagnóstico por imagem , Hiperemia/patologia , Necrose , Valor Preditivo dos Testes
8.
Toxicol Lett ; 332: 181-191, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32473956

RESUMO

Trans-1233zd was developed as a refrigerant and propellant in consumer products; its toxicity has been studied extensively. The scope of this assessment is to apply the confirmed NOAEC to conduct Benchmark Dose Modeling (BMD) and determine the Point of Departure (POD). In a previously published 13-week inhalation study, a NOAEC was identified at 4000 ppm. Due to uncertainty concerning the cardiac lesion, an external pathology peer review of heart tissues was undertaken using published best practices and consistent nomenclature and diagnostic criteria. The cardiac lesion observed at 4000 ppm was considered to be spontaneous based on lesion location and microscopic features. BMD was applied to derive the BMDL05 and BMDL10; the more conservative BMDL05 was used as the POD for risk assessment to calculate the Reference Exposure Levels (RELs). The 2-Box Air Dispersion Model was used to calculate the exposure to consumer products. Both the acute and chronic exposure concentrations calculated were compared to the acute and chronic RELs. The acute and chronic exposure to trans-1233zd in the assessed consumer products are below the RELs and deemed safe for their intended uses.


Assuntos
Clorofluorcarbonetos de Metano/toxicidade , Clorofluorcarbonetos/toxicidade , Administração por Inalação , Animais , Benchmarking , Relação Dose-Resposta a Droga , Exposição Ambiental , Feminino , Cardiopatias/induzido quimicamente , Cardiopatias/patologia , Exposição por Inalação , Masculino , Modelos Biológicos , Nível de Efeito Adverso não Observado , Ratos , Ratos Sprague-Dawley , Medição de Risco
10.
Cardiovasc Pathol ; 48: 107233, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32434133

RESUMO

This paper collates the pathological findings from initial published autopsy reports on 23 patients with coronavirus disease 2019 (COVID-19) from 5 centers in the United States of America, including 3 cases from Houston, Texas. Findings confirm that COVID-19 is a systemic disease with major involvement of the lungs and heart. Acute COVID-19 pneumonia has features of a distinctive acute interstitial pneumonia with a diffuse alveolar damage component, coupled with microvascular involvement with intra- and extravascular fibrin deposition and intravascular trapping of neutrophils, and, frequently, with formation of microthombi in arterioles. Major pulmonary thromboemboli with pulmonary infarcts and/or hemorrhage occurred in 5 of the 23 patients. Two of the Houston cases had interstitial pneumonia with diffuse alveolar damage pattern. One of the Houston cases had multiple bilateral segmental pulmonary thromboemboli with infarcts and hemorrhages coupled with, in nonhemorrhagic areas, a distinctive interstitial lymphocytic pneumonitis with intra-alveolar fibrin deposits and no hyaline membranes, possibly representing a transition form to acute fibrinous and organizing pneumonia. Multifocal acute injury of cardiac myocytes was frequently observed. Lymphocytic myocarditis was reported in 1 case. In addition to major pulmonary pathology, the 3 Houston cases had evidence of lymphocytic pericarditis, multifocal acute injury of cardiomyocytes without inflammatory cellular infiltrates, depletion of splenic white pulp, focal hepatocellular degeneration and rare glomerular capillary thrombosis. Each had evidence of chronic cardiac disease: hypertensive left ventricular hypertrophy (420 g heart), dilated cardiomyopathy (1070 g heart), and hypertrophic cardiomyopathy (670 g heart). All 3 subjects were obese (BMIs of 33.8, 51.65, and 35.2 Kg/m2). Overall, the autopsy findings support the concept that the pathogenesis of severe COVID-19 disease involves direct viral-induced injury of multiple organs, including heart and lungs, coupled with the consequences of a procoagulant state with coagulopathy.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/patologia , Cardiopatias/patologia , Pulmão/patologia , Miocárdio/patologia , Pneumonia Viral/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Feminino , Nível de Saúde , Coração/virologia , Cardiopatias/mortalidade , Cardiopatias/virologia , Interações Hospedeiro-Patógeno , Humanos , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Fatores de Risco , Estados Unidos/epidemiologia
11.
Am J Physiol Cell Physiol ; 319(1): C166-C182, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32432929

RESUMO

This review aims to highlight the normal physiological remodeling that occurs in healthy aging hearts, including changes that occur in contractility, conduction, valve function, large and small coronary vessels, and the extracellular matrix. These "normal" age-related changes serve as the foundation that supports decreased plasticity and limited ability for tissue remodeling during pathophysiological states such as myocardial ischemia and heart failure. This review will identify populations at greater risk for poor tissue remodeling in advanced age along with present and future therapeutic strategies that may ameliorate dysfunctional tissue remodeling in aging hearts.


Assuntos
Envelhecimento Saudável/patologia , Cardiopatias/patologia , Miocárdio/patologia , Remodelação Ventricular/fisiologia , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Envelhecimento Saudável/metabolismo , Cardiopatias/metabolismo , Humanos , Miocárdio/metabolismo
14.
J Cancer Res Ther ; 16(1): 53-59, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32362609

RESUMO

Aim of Study: Cardiac complications may be observed after hematopoietic stem cell transplantation (HSCT). Despite significant improvement in supportive care, HSCT may be associated with significant morbidity and mortality. In this study, the aim was to evaluate the frequency of clinically serious cardiac complications after HSCT in our patients. Materials and Methods: This is a retrospective study. Cardiac complications were analyzed in 75 patients undergone to HSCT with physical examination, electrocardiography, echocardiography, and cardiac monitorization. Results: The median age was 12 years (range 11-16) and M/F ratio was 2/3 = 0.66. There are five patients with six complications among the retrospective cohort of 75. These were pericardial effusion in three patients, and sinus bradycardia in two patients and ventricular tachycardia in one patient. The incidence of cardiac complications among 75 patients with HSCT was 6.7%. The mortality rates of patients with and without cardiac complication were 40% and 34%, and both of them with cardiac complication had pericardial effusion. However, the cardiac complication was not found statistically significant factor on survival ( P = 0.82). Conclusion: Poor risk factors of patients, myocarditis, pericarditis, and heart failure owing to cumulative doses of anthracycline, cyclophosphamide, cytomegalovirus infection or other infections, mediastinal irradiation, and cryopreserved stem cell product with dimethyl sulfoxide may be effective on the development of cardiac complications individually. Early intervention can prevent death related to this complication.


Assuntos
Arritmias Cardíacas/patologia , Cardiopatias/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Neoplasias/terapia , Condicionamento Pré-Transplante/efeitos adversos , Adolescente , Arritmias Cardíacas/etiologia , Criança , Ecocardiografia/métodos , Feminino , Cardiopatias/etiologia , Humanos , Masculino , Neoplasias/patologia , Estudos Retrospectivos
15.
Int J Cardiovasc Imaging ; 36(9): 1761-1769, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32409978

RESUMO

Right ventricular biopsy represents the gold standard for the assessment of myocardial fibrosis and collagen content. This invasive technique, however, is accompanied by perioperative complications and poor reproducibility. Extracellular volume (ECV) measured through cardiovascular magnetic resonance (CMR) has emerged as a valid surrogate method to assess fibrosis non-invasively. Nonetheless, ECV provides an overestimation of collagen concentration since it also considers interstitial space. Our study aims to investigate the feasibility of estimating total collagen volume (TCV) through CMR by comparing it with the TCV measured at histology. Seven healthy Landrace pigs were acutely instrumented closed-chest and transported to the MRI facility for measurements. For each protocol, CMR imaging at 3T was acquired. MEDIS software was used to analyze T1 mapping and ECV for both the left ventricular myocardium (LVmyo) and left ventricular septum (LVseptum). ECV was then used to estimate TCVCMR at LVmyo and LVseptum following previously published formulas. Tissues were prepared following an established protocol and stained with picrosirius red to analyze the TCVhisto in LVmyo and LVseptum. TCV measured at LVmyo and LVseptum with both histology (8 ± 5 ml and 7 ± 3 ml, respectively) and T1-Mapping (9 ± 5 ml and 8 ± 6 ml, respectively) did not show any regional differences. TCVhisto and TCVCMR showed a good level of data agreement by Bland-Altman analysis. Estimation of TCV through CMR may be a promising way to non-invasively assess myocardial collagen content and may be useful to track disease progression or treatment response.


Assuntos
Colágeno/análise , Cardiopatias/diagnóstico por imagem , Coração/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Miocárdio/química , Animais , Biópsia , Estudos de Viabilidade , Fibrose , Cardiopatias/metabolismo , Cardiopatias/patologia , Miocárdio/patologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Sus scrofa
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.
PLoS One ; 15(4): e0231905, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32315372

RESUMO

Myocardial fibrosis is often associated with cardiac hypertrophy; indeed, fibrosis is one of the most critical factors affecting prognosis. We aimed to identify the molecules involved in promoting fibrosis under hypertrophic stimuli. We previously established a rat model of cardiac hypertrophy by pulmonary artery banding, in which approximately half of the animals developed fibrosis in the right ventricle. Here, we first comprehensively analyzed mRNA expression in the right ventricle with or without fibrosis in pulmonary artery banding model rats by DNA microarray analysis (GSE141650 at NCBI GEO). The expression levels of 19 genes were up-regulated more than 1.5-fold in fibrotic hearts compared with non-fibrotic hearts. Among them, fibrosis growth factor (FGF) 23 showed one of the biggest increases in expression. Real-time PCR analysis also revealed that, among the FGF receptor (FGFR) family, FGFR1 was highly expressed in fibrotic hearts. We then found that FGF23 was expressed predominantly in cardiomyocytes, while FGFR1 was predominantly expressed in fibroblasts in the rat ventricle. Next, we added FGF23 and transforming growth factor (TGF)-ß1 (10-50 ng/mL of each) to isolated fibroblasts from normal adult rat ventricles and cultured them for three days. While FGF23 itself did not directly affect the expression levels of any fibrosis-related mRNAs, FGF23 enhanced the effect of TGF-ß1 on increasing the expression levels of α-smooth muscle actin (α-SMA) mRNA. This increase in xx-SMA mRNA levels due to the combination of TGF-ß1 and FGF23 was attenuated by the inhibition of FGFR1 or the knockdown of FGFR1 in fibroblasts. Thus, FGF23 synergistically promoted the activation of fibroblasts with TGF-ß1, transforming fibroblasts into myofibroblasts via FGFR1. Thus, we identified FGF23 as a paracrine factor secreted from cardiomyocytes to promote cardiac fibrosis under conditions in which TGF-ß1 is activated. FGF23 could be a possible target to prevent fibrosis following myocardial hypertrophy.


Assuntos
Fatores de Crescimento de Fibroblastos/farmacologia , Cardiopatias/patologia , Fator de Crescimento Transformador beta1/farmacologia , Regulação para Cima/efeitos dos fármacos , Actinas/genética , Actinas/metabolismo , Animais , Células Cultivadas , Modelos Animais de Doenças , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Fibrose , Cardiopatias/metabolismo , Masculino , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Pirróis/farmacologia , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo
18.
PLoS One ; 15(4): e0231100, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32255803

RESUMO

BACKGROUND: Elective percutaneous coronary interventions (PCI) are difficult to discriminate from non-elective PCI in administrative data due to non-specific encounter codes, limiting the ability to track outcomes, ensure appropriate medical management, and/or perform research on patients who undergo elective PCI. The objective of this study was to assess the abilities of several algorithms to identify elective PCI procedures using administrative data containing diagnostic, utilization, and/or procedural codes. METHODS AND RESULTS: For this retrospective study, administrative databases in an integrated healthcare delivery system were queried between 1/1/2015 and 6/31/2016 to identify patients who had an encounter for a PCI. Using clinical criteria, each encounter was classified via chart review as a valid PCI, then as elective or non-elective. Cases were tested against nine pre-determined algorithms. Performance statistics (sensitivity, specificity, positive predictive value, and negative predictive value) and associated 95% confidence intervals (CI) were calculated. Of 521 PCI encounters reviewed, 497 were valid PCI, 93 of which were elective. An algorithm that excluded emergency room visit events had the highest sensitivity (97.9%, 95%CI 92.5%-99.7%) while an algorithm that included events occurring within 90 days of a cardiologist visit and coronary angiogram or stress test had the highest positive predictive value (62.2%, 95%CI 50.8%-72.7%). CONCLUSIONS: Without an encounter code specific for elective PCI, an algorithm excluding procedures associated with an emergency room visit had the highest sensitivity to identify elective PCI. This offers a reasonable approach to identify elective PCI from administrative data.


Assuntos
Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Cardiopatias/cirurgia , Intervenção Coronária Percutânea/estatística & dados numéricos , Adolescente , Adulto , Idoso , Algoritmos , Angiografia Coronária , Bases de Dados Factuais , Teste de Esforço/métodos , Feminino , Cardiopatias/diagnóstico por imagem , Cardiopatias/epidemiologia , Cardiopatias/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
19.
Virchows Arch ; 476(6): 797-820, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32266476

RESUMO

The adult congenital heart diseases (ACHD) population is exceeding the pediatric congenital heart diseases (CHD) population and is progressively expanding each year, representing more than 90% of patients with CHD. Of these, about 75% have undergone surgical and/or percutaneous intervention for palliation or correction. Autopsy can be a very challenging procedure in ACHD patients. The approach and protocol to be used may vary depending on whether the pathologists are facing native disease without surgical or percutaneous interventions, but with various degrees of cardiac remodeling, or previously palliated or corrected CHD. Moreover, interventions for the same condition have evolved over the last decades, as has perioperative myocardial preservations and postoperative care, with different long-term sequelae depending on the era in which patients were operated on. Careful clinicopathological correlation is, thus, required to assist the pathologist in performing the autopsy and reaching a diagnosis regarding the cause of death. Due to the heterogeneity of the structural abnormalities, and the wide variety of surgical and interventional procedures, there are no standard methods for dissecting the heart at autopsy. In this paper, we describe the most common types of CHDs that a pathologist could encounter at autopsy, including the various types of surgical and percutaneous procedures and major pathological manifestations. We also propose a practical systematic approach to the autopsy of ACHD patients.


Assuntos
Cardiopatias/patologia , Adulto , Autopsia , Cardiopatias/congênito , Cardiopatias/diagnóstico , Humanos , Miocárdio/patologia
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