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1.
Front Endocrinol (Lausanne) ; 12: 726967, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484128

RESUMO

In March 2020, the WHO declared coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a global pandemic. Obesity was soon identified as a risk factor for poor prognosis, with an increased risk of intensive care admissions and mechanical ventilation, but also of adverse cardiovascular events. Obesity is associated with adipose tissue, chronic low-grade inflammation, and immune dysregulation with hypertrophy and hyperplasia of adipocytes and overexpression of pro-inflammatory cytokines. However, to implement appropriate therapeutic strategies, exact mechanisms must be clarified. The role of white visceral adipose tissue, increased in individuals with obesity, seems important, as a viral reservoir for SARS-CoV-2 via angiotensin-converting enzyme 2 (ACE2) receptors. After infection of host cells, the activation of pro-inflammatory cytokines creates a setting conducive to the "cytokine storm" and macrophage activation syndrome associated with progression to acute respiratory distress syndrome. In obesity, systemic viral spread, entry, and prolonged viral shedding in already inflamed adipose tissue may spur immune responses and subsequent amplification of a cytokine cascade, causing worse outcomes. More precisely, visceral adipose tissue, more than subcutaneous fat, could predict intensive care admission; and lower density of epicardial adipose tissue (EAT) could be associated with worse outcome. EAT, an ectopic adipose tissue that surrounds the myocardium, could fuel COVID-19-induced cardiac injury and myocarditis, and extensive pneumopathy, by strong expression of inflammatory mediators that could diffuse paracrinally through the vascular wall. The purpose of this review is to ascertain what mechanisms may be involved in unfavorable prognosis among COVID-19 patients with obesity, especially cardiovascular events, emphasizing the harmful role of excess ectopic adipose tissue, particularly EAT.


Assuntos
COVID-19/metabolismo , Cardiomiopatias/metabolismo , Gordura Intra-Abdominal/metabolismo , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/complicações , COVID-19/imunologia , Cardiomiopatias/imunologia , Cardiomiopatias/patologia , Cardiopatias/imunologia , Cardiopatias/metabolismo , Cardiopatias/patologia , Humanos , Inflamação , Gordura Intra-Abdominal/patologia , Obesidade/complicações , Obesidade/imunologia , Obesidade/patologia , Pericárdio , Prognóstico , SARS-CoV-2/metabolismo , Serina Endopeptidases/metabolismo
3.
Viruses ; 13(6)2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071557

RESUMO

Patients with underlying cardiovascular conditions are particularly vulnerable to severe COVID-19. In this project, we aimed to characterize similarities in dysregulated immune pathways between COVID-19 patients and patients with cardiomyopathy, venous thromboembolism (VTE), or coronary artery disease (CAD). We hypothesized that these similarly dysregulated pathways may be critical to how cardiovascular diseases (CVDs) exacerbate COVID-19. To evaluate immune dysregulation in different diseases, we used four separate datasets, including RNA-sequencing data from human left ventricular cardiac muscle samples of patients with dilated or ischemic cardiomyopathy and healthy controls; RNA-sequencing data of whole blood samples from patients with single or recurrent event VTE and healthy controls; RNA-sequencing data of human peripheral blood mononuclear cells (PBMCs) from patients with and without obstructive CAD; and RNA-sequencing data of platelets from COVID-19 subjects and healthy controls. We found similar immune dysregulation profiles between patients with CVDs and COVID-19 patients. Interestingly, cardiomyopathy patients display the most similar immune landscape to COVID-19 patients. Additionally, COVID-19 patients experience greater upregulation of cytokine- and inflammasome-related genes than patients with CVDs. In all, patients with CVDs have a significant overlap of cytokine- and inflammasome-related gene expression profiles with that of COVID-19 patients, possibly explaining their greater vulnerability to severe COVID-19.


Assuntos
COVID-19/imunologia , COVID-19/fisiopatologia , Cardiomiopatias/imunologia , Doença da Artéria Coronariana/imunologia , Tromboembolia Venosa/imunologia , COVID-19/complicações , COVID-19/genética , Cardiomiopatias/complicações , Cardiomiopatias/genética , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/genética , Citocinas/genética , Conjuntos de Dados como Assunto , Humanos , Hospedeiro Imunocomprometido/genética , Inflamassomos/genética , Contagem de Linfócitos , Gravidade do Paciente , RNA-Seq , Tromboembolia Venosa/complicações
4.
Front Immunol ; 12: 624703, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33692798

RESUMO

Accumulating evidence suggests that the breakdown of immune tolerance plays an important role in the development of myocarditis triggered by cardiotropic microbial infections. Genetic deletion of immune checkpoint molecules that are crucial for maintaining self-tolerance causes spontaneous myocarditis in mice, and cancer treatment with immune checkpoint inhibitors can induce myocarditis in humans. These results suggest that the loss of immune tolerance results in myocarditis. The tissue microenvironment influences the local immune dysregulation in autoimmunity. Recently, tenascin-C (TN-C) has been found to play a role as a local regulator of inflammation through various molecular mechanisms. TN-C is a nonstructural extracellular matrix glycoprotein expressed in the heart during early embryonic development, as well as during tissue injury or active tissue remodeling, in a spatiotemporally restricted manner. In a mouse model of autoimmune myocarditis, TN-C was detectable before inflammatory cell infiltration and myocytolysis became histologically evident; it was strongly expressed during active inflammation and disappeared with healing. TN-C activates dendritic cells to generate pathogenic autoreactive T cells and forms an important link between innate and acquired immunity.


Assuntos
Doenças Autoimunes/metabolismo , Autoimunidade , Cardiomiopatias/metabolismo , Mediadores da Inflamação/metabolismo , Miocardite/metabolismo , Miocárdio/metabolismo , Tenascina/metabolismo , Animais , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Cardiomiopatias/imunologia , Cardiomiopatias/patologia , Microambiente Celular , Humanos , Miocardite/imunologia , Miocardite/patologia , Miocárdio/imunologia , Miocárdio/patologia , Tolerância a Antígenos Próprios , Transdução de Sinais
5.
Mol Biol Cell ; 32(7): 622-633, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33534612

RESUMO

Dysregulation of immune responses has been linked to the generation of immunoglobulin G (IgG) autoantibodies that target human ß1ARs and contribute to deleterious cardiac outcomes. Given the benefits of ß-blockers observed in patients harboring the IgG3 subclass of autoantibodies, we investigated the role of these autoantibodies in human ß1AR function. Serum and purified IgG3(+) autoantibodies from patients with onset of cardiomyopathy were tested using human embryonic kidney (HEK) 293 cells expressing human ß1ARs. Unexpectedly, pretreatment of cells with IgG3(+) serum or purified IgG3(+) autoantibodies impaired dobutamine-mediated adenylate cyclase (AC) activity and cyclic adenosine monophosphate (cAMP) generation while enhancing biased ß-arrestin recruitment and Extracellular Regulated Kinase (ERK) activation. In contrast, the ß-blocker metoprolol increased AC activity and cAMP in the presence of IgG3(+) serum or IgG3(+) autoantibodies. Because IgG3(+) autoantibodies are specific to human ß1ARs, non-failing human hearts were used as an endogenous system to determine their ability to bias ß1AR signaling. Consistently, metoprolol increased AC activity, reflecting the ability of the IgG3(+) autoantibodies to bias ß-blocker toward G-protein coupling. Importantly, IgG3(+) autoantibodies are specific toward ß1AR as they did not alter ß2AR signaling. Thus, IgG3(+) autoantibody biases ß-blocker toward G-protein coupling while impairing agonist-mediated G-protein activation but promoting G-protein-independent ERK activation. This phenomenon may underlie the beneficial outcomes observed in patients harboring IgG3(+) ß1AR autoantibodies.


Assuntos
Autoanticorpos/imunologia , Imunoglobulina G/imunologia , Receptores Adrenérgicos beta 1/imunologia , Autoanticorpos/sangue , Cardiomiopatias/imunologia , Cardiomiopatias/fisiopatologia , AMP Cíclico , Células HEK293 , Coração/fisiologia , Humanos , Imunoglobulina G/metabolismo , Receptores Adrenérgicos/imunologia , Receptores Adrenérgicos beta 1/metabolismo , Transdução de Sinais , beta-Arrestinas
6.
PLoS Biol ; 19(1): e3001062, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33395408

RESUMO

Lyme carditis is an extracutaneous manifestation of Lyme disease characterized by episodes of atrioventricular block of varying degrees and additional, less reported cardiomyopathies. The molecular changes associated with the response to Borrelia burgdorferi over the course of infection are poorly understood. Here, we identify broad transcriptomic and proteomic changes in the heart during infection that reveal a profound down-regulation of mitochondrial components. We also describe the long-term functional modulation of macrophages exposed to live bacteria, characterized by an augmented glycolytic output, increased spirochetal binding and internalization, and reduced inflammatory responses. In vitro, glycolysis inhibition reduces the production of tumor necrosis factor (TNF) by memory macrophages, whereas in vivo, it produces the reversion of the memory phenotype, the recovery of tissue mitochondrial components, and decreased inflammation and spirochetal burdens. These results show that B. burgdorferi induces long-term, memory-like responses in macrophages with tissue-wide consequences that are amenable to be manipulated in vivo.


Assuntos
Borrelia burgdorferi/imunologia , Cardiomiopatias/etiologia , Memória Imunológica , Doença de Lyme/imunologia , Macrófagos/fisiologia , Animais , Cardiomiopatias/imunologia , Cardiomiopatias/microbiologia , Cardiomiopatias/patologia , Células Cultivadas , Endocardite Bacteriana/complicações , Endocardite Bacteriana/imunologia , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/patologia , Feminino , Células HEK293 , Coração/microbiologia , Humanos , Doença de Lyme/patologia , Ativação de Macrófagos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/imunologia , Miócitos Cardíacos/microbiologia , Miócitos Cardíacos/patologia , Células RAW 264.7
7.
Cardiovasc Pathol ; 51: 107315, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33264681

RESUMO

There are few reports on the coexistence of cardiac amyloid light-chain (AL) amyloidosis and light chain deposition disease (LCDD), despite their similar pathophysiologies caused by plasma-cell dyscrasia. Herein, we report the coexistence of these diseases. A 59-year-old man was referred to our hospital because of exertional dyspnea and hypotension. Renal dysfunction of unknown etiology had been present for 4 years and hemodialysis had been introduced. Severe systolic and diastolic cardiac dysfunction was apparent, accompanied with dilatation and granular sparkling, but not with left ventricular hypertrophy. The plasma-free light chain κ was found to be extremely high, with a κ/λ ratio of 1,919. Light microscopic examination of the endomyocardial biopsy revealed spotty and homogenous deposits, which positively stained with Congo red, and exhibited a blazing apple-green color under polarized light. Based on these results, cardiac amyloidosis was diagnosed. In specimens prepared for electron microscopy, no amyloid fibrils could be found. Instead, we observed amorphous nonfibrillar deposits around several small vessels including capillaries and small arteries, which were consistent with light-chain deposits. LCDD was diagnosed based on the systemic increase in κ light chain and the ultrastructural findings of the endomyocardial biopsy specimens. Coexistence of cardiac amyloidosis and LCDD was thus confirmed in our patient. An electron microscopic assessment in addition to Congo red staining may be useful to diagnose latent LCDD in patients with suspected cardiac light-chain amyloidosis.


Assuntos
Cardiomiopatias/patologia , Cadeias Leves de Imunoglobulina/ultraestrutura , Amiloidose de Cadeia Leve de Imunoglobulina/patologia , Miocárdio/ultraestrutura , Biópsia , Cardiomiopatias/imunologia , Cardiomiopatias/terapia , Evolução Fatal , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/imunologia , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Miocárdio/imunologia
8.
Int Immunopharmacol ; 90: 107160, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33243604

RESUMO

Septic cardiomyopathy (SCM)is common in septic patients and results in cardiovascular failure. The pathogenesis of SCM is complicated, and patients with SCM have high mortality because current treatment methods are limited. The cholinergic anti-inflammatory pathway (CAP) modulates inflammatory responses through vagus nerve stimulation that leads to the release of acetylcholine (ACh), which binds to the alpha7 nicotinic acetylcholine receptor (α7nAChR). Moreover, α7nAChR activation by its agonists at the tissue level inhibits inflammatory mediators and regulates the function of immune cells in sepsis. Therefore, the α7nAChR can maintain balance of the inflammatory-immune response in sepsis. CAP has been elucidated as a critical regulator of anti-inflammation in many diseases, including rheumatoid arthritis, inflammatory boweldisease and SCM. Additionally, some clinical and preclinical trials show therapeutic potential via regulating CAP. There are excellent studies regarding the beneficial role of CAP activation, especially α7nAChR, in experimental SCM. This review aims to discuss the CAP in attenuating inflammation and the potential role of α7nAChR activation in regulating immune and reducing inflammation in SCM.


Assuntos
Cardiomiopatias/imunologia , Cardiomiopatias/metabolismo , Neuroimunomodulação/imunologia , Neuroimunomodulação/fisiologia , Animais , Humanos , Inflamação/metabolismo , Camundongos , Ratos , Sepse , Receptor Nicotínico de Acetilcolina alfa7/metabolismo
9.
Nat Rev Cardiol ; 18(3): 169-193, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33046850

RESUMO

Inflammatory cardiomyopathy, characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function, has a heterogeneous aetiology. Inflammatory cardiomyopathy is predominantly mediated by viral infection, but can also be induced by bacterial, protozoal or fungal infections as well as a wide variety of toxic substances and drugs and systemic immune-mediated diseases. Despite extensive research, inflammatory cardiomyopathy complicated by left ventricular dysfunction, heart failure or arrhythmia is associated with a poor prognosis. At present, the reason why some patients recover without residual myocardial injury whereas others develop dilated cardiomyopathy is unclear. The relative roles of the pathogen, host genomics and environmental factors in disease progression and healing are still under discussion, including which viruses are active inducers and which are only bystanders. As a consequence, treatment strategies are not well established. In this Review, we summarize and evaluate the available evidence on the pathogenesis, diagnosis and treatment of myocarditis and inflammatory cardiomyopathy, with a special focus on virus-induced and virus-associated myocarditis. Furthermore, we identify knowledge gaps, appraise the available experimental models and propose future directions for the field. The current knowledge and open questions regarding the cardiovascular effects associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are also discussed. This Review is the result of scientific cooperation of members of the Heart Failure Association of the ESC, the Heart Failure Society of America and the Japanese Heart Failure Society.


Assuntos
Cardiomiopatias/fisiopatologia , Inflamação/fisiopatologia , Miocardite/fisiopatologia , Viroses/fisiopatologia , Animais , Antivirais/uso terapêutico , Autoimunidade/imunologia , Biópsia , COVID-19/fisiopatologia , COVID-19/terapia , Cardiomiopatias/diagnóstico , Cardiomiopatias/imunologia , Cardiomiopatias/terapia , Cardiomiopatia Dilatada , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Infecções por Coxsackievirus/imunologia , Infecções por Coxsackievirus/fisiopatologia , Infecções por Coxsackievirus/terapia , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/fisiopatologia , Infecções por Citomegalovirus/terapia , Modelos Animais de Doenças , Infecções por Echovirus/imunologia , Infecções por Echovirus/fisiopatologia , Infecções por Echovirus/terapia , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/fisiopatologia , Infecções por Vírus Epstein-Barr/terapia , Eritema Infeccioso/imunologia , Eritema Infeccioso/fisiopatologia , Eritema Infeccioso/terapia , Infecções por HIV/fisiopatologia , Hepatite C/imunologia , Hepatite C/fisiopatologia , Hepatite C/terapia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Inflamação/diagnóstico , Inflamação/imunologia , Inflamação/terapia , Influenza Humana/imunologia , Influenza Humana/fisiopatologia , Influenza Humana/terapia , Leucócitos/imunologia , Miocardite/diagnóstico , Miocardite/imunologia , Miocardite/terapia , Miocárdio/patologia , Prognóstico , Infecções por Roseolovirus/imunologia , Infecções por Roseolovirus/fisiopatologia
10.
Rheumatology (Oxford) ; 60(8): 3809-3816, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-33369674

RESUMO

OBJECTIVE: Myocardial involvement (MCI) is known to increase morbidity and mortality in polymyositis (PM) and dermatomyositis (DM). This study aims to investigate whether complicating with ventricular arrhythmia (VA) predicts poor outcomes in patients with PM/DM-related myocardial involvement (PM/DM-MCI). METHODS: We reviewed all PM/DM-MCI patients admitted to Peking Union Medical College Hospital from October 1997 to April 2019. VA and the other possible risk factors for the composite endpoint, including death from any cause and rehospitalization for cardiac causes, were analyzed. RESULTS: A total of 75 PM/DM-MCI patients (44 PM and 31 DM) were enrolled, of which 27 (36%) met the composite endpoint during a median follow-up of 24 months. Independent prognostic factors for the composite endpoint include VA [HR 4.215, 95% CI (1.737, 10.230)], NT-proBNP > 3415 pg/ml [HR 2.606, 95% CI (1.203, 5.646)], interstitial lung disease [HR 2.688, 95% CI (1.209, 5.978)], and anti-cardiac remodelling therapy [HR 0.302, 95% CI (0.115, 0.792)]. The 3-year event-free survival rate of patients without VA was significantly higher than that of patients with VA (63.3% vs 40.7%, P = 0.034). Skin lesions [OR 0.163, 95% CI (0.051, 0.523)] and positive antimitochondrial antibody [OR 3.484, 95% CI (1.192, 10.183)] were independent predictors of VA. CONCLUSION: VA provides prognostic insights for PM/DM-MCI patients and predicts poor outcome. Polymyositis and positive antimitochondrial antibody are closely associated with the presence of VA in PM/DM-MCI.


Assuntos
Arritmias Cardíacas/fisiopatologia , Cardiomiopatias/fisiopatologia , Dermatomiosite/fisiopatologia , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Arritmias Cardíacas/epidemiologia , Autoanticorpos/imunologia , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/epidemiologia , Cardiomiopatias/imunologia , Dermatomiosite/tratamento farmacológico , Dermatomiosite/epidemiologia , Dermatomiosite/imunologia , Feminino , Humanos , Doenças Pulmonares Intersticiais/epidemiologia , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Mitocôndrias/imunologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Polimiosite/tratamento farmacológico , Polimiosite/epidemiologia , Polimiosite/imunologia , Polimiosite/fisiopatologia , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Espironolactona/uso terapêutico , Taxa de Sobrevida
12.
Int J Mol Sci ; 21(18)2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899712

RESUMO

Cardiomyopathies (CMPs) represent a diverse group of heart muscle diseases, grouped into specific morphological and functional phenotypes. CMPs are associated with mutations in sarcomeric and non-sarcomeric genes, with several suspected epigenetic and environmental mechanisms involved in determining penetrance and expressivity. The understanding of the underlying molecular mechanisms of myocardial diseases is fundamental to achieving a proper management and treatment of these disorders. Among these, inflammation seems to play an important role in the pathogenesis of CMPs. The aim of the present study is to review the current knowledge on the role of inflammation and the immune system activation in the pathogenesis of CMPs and to identify potential molecular targets for a tailored anti-inflammatory treatment.


Assuntos
Cardiomiopatias/imunologia , Cardiomiopatias/fisiopatologia , Inflamação/imunologia , Animais , Cardiomiopatias/genética , Humanos , Inflamação/patologia , Mutação , Fenótipo , Sarcômeros
13.
Nat Med ; 26(11): 1701-1707, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32812012

RESUMO

Recent reports highlight a new clinical syndrome in children related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1-multisystem inflammatory syndrome in children (MIS-C)-which comprises multiorgan dysfunction and systemic inflammation2-13. We performed peripheral leukocyte phenotyping in 25 children with MIS-C, in the acute (n = 23; worst illness within 72 h of admission), resolution (n = 14; clinical improvement) and convalescent (n = 10; first outpatient visit) phases of the illness and used samples from seven age-matched healthy controls for comparisons. Among the MIS-C cohort, 17 (68%) children were SARS-CoV-2 seropositive, suggesting previous SARS-CoV-2 infections14,15, and these children had more severe disease. In the acute phase of MIS-C, we observed high levels of interleukin-1ß (IL-1ß), IL-6, IL-8, IL-10, IL-17, interferon-γ and differential T and B cell subset lymphopenia. High CD64 expression on neutrophils and monocytes, and high HLA-DR expression on γδ and CD4+CCR7+ T cells in the acute phase, suggested that these immune cell populations were activated. Antigen-presenting cells had low HLA-DR and CD86 expression, potentially indicative of impaired antigen presentation. These features normalized over the resolution and convalescence phases. Overall, MIS-C presents as an immunopathogenic illness1 and appears distinct from Kawasaki disease.


Assuntos
COVID-19/sangue , COVID-19/imunologia , Leucócitos/classificação , Leucócitos/patologia , SARS-CoV-2/imunologia , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Adolescente , Idade de Início , Coagulação Sanguínea/fisiologia , COVID-19/complicações , COVID-19/epidemiologia , Cardiomiopatias/sangue , Cardiomiopatias/etiologia , Cardiomiopatias/imunologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Imunofenotipagem , Inflamação/sangue , Inflamação/etiologia , Inflamação/imunologia , Leucócitos/imunologia , Masculino , Síndrome de Resposta Inflamatória Sistêmica/complicações , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia
14.
J Investig Med High Impact Case Rep ; 8: 2324709620947577, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32762374

RESUMO

A 66-year-old male patient with coronavirus disease-19 (COVID-19) developed cardiogenic shock with echocardiographic evidence of decreased left ventricular ejection fraction and global hypokinesia concomitant with a robust systemic inflammatory response. Following the administration of convalescent plasma therapy and inotropic support, left ventricular function recovered fully in accordance with the decrease in the concentration of the inflammatory markers. Thus, we demonstrate the presence of transient reversible cardiomyopathy in a patient with severe COVID-19 and illustrate the association of acute cardiac dysfunction with profound systemic inflammation among COVID-19 patients.


Assuntos
Betacoronavirus , Cardiomiopatias/terapia , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Idoso , COVID-19 , Cardiomiopatias/complicações , Cardiomiopatias/imunologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Humanos , Imunização Passiva/métodos , Masculino , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , SARS-CoV-2 , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda
15.
J Fish Dis ; 43(8): 955-962, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32608050

RESUMO

During the last decade, Piscine orthoreovirus was identified as the main causative agent of heart and skeletal muscle inflammation (HSMI) in Atlantic Salmon, Norway. A recent study showed that PRV-1 sequences from salmonid collected in North Atlantic Pacific Coast (NAPC) grouped separately from the Norwegian sequences found in Atlantic Salmon diagnosed with HSMI. Currently, the routine assay used to screen for PRV-1 in NAPC water and worldwide cannot differentiate between the two groups of PRV-1. Therefore, this study aimed at developing a real-time polymerase chain reaction (RT-qPCR) assay to target the PRV-1 genome segments specific for variants associated with HSMI. The assay was optimized and tested against 71 tissue samples collected from different regions including Norway, Chile and both coast of Canada and different hosts farmed Atlantic Salmon, wild Coho Salmon and escaped Atlantic Salmon collected in British Columbia, West Coast of Canada. This assay has the potential to be used for screening salmonids and non-salmonids that may carry PRV-1 potentially causing HSMI.


Assuntos
Cardiomiopatias/veterinária , Doenças dos Peixes/virologia , Inflamação/veterinária , Doenças Musculares/veterinária , Orthoreovirus/genética , Infecções por Reoviridae/veterinária , Salmo salar , Animais , Canadá , Cardiomiopatias/imunologia , Chile , Doenças dos Peixes/imunologia , Inflamação/imunologia , Inflamação/virologia , Músculo Esquelético/imunologia , Doenças Musculares/imunologia , Miocárdio/imunologia , Noruega , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Infecções por Reoviridae/imunologia , Infecções por Reoviridae/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária
16.
BMC Cardiovasc Disord ; 20(1): 269, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503464

RESUMO

BACKGROUND: Peripartum cardiomyopathy (PPCM) is life-threatening heart disease. However, the causes and pathogenesis of PPCM remain unclear. Previous studies found that ß1 adrenoceptor antibodies (ß1AA) had possible involvement in the development of PPCM. In the present study, we determined the potential relationship between PPCM and ß1AA, including the mechanism of ß1AA leading to PPCM. METHODS: We extracted the ß1AA from the postpartum Wistar rats that were injected by the antigen peptide segment of the ß1 adrenoceptor to produce PPCM. We tested the effects of ß1AA on H9C2 cell line by CCK-8, LDH, TUNEL, SA-ELISA, qRT-PCR, and western blot methods. Furthermore, PGC-1α was overexpressed to rescue the effect of ß1AA on H9C2 cells. RESULTS: We found that the extracted ß1AA induced apoptosis of cardiac myocytes of H9C2 cell line. Moreover, the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), which is a master regulator of mitochondrial metabolism, and its downstream transcript vascular endothelial growth factor (VEGF) got decreased in H9C2 cells after ß1AA treatment. In addition, the effect of ß1AA could be inhibited by atenolol, the antagonist of ß1 adrenoceptors (ß1AR) and imitated by isoprenaline, the agonist of ß1AR. Furthermore, overexpression of PGC-1α in the H9C2 cells rescued the apoptosis of cells and inhibitory expression of VEGF induced by ß1AA. CONCLUSIONS: Our results suggest that the symptoms of PPCM due to myocardial cell apoptosis induced by ß1AA inhibiting the PGC-1α-related pathway impairs mitochondrial energy metabolism. Therefore, our results uncover a previously unknown role of the ß1AA pathway in the etiology of PPCM and provide a novel potential target for the treatment of PPCM.


Assuntos
Anticorpos/imunologia , Apoptose , Cardiomiopatias/imunologia , Miócitos Cardíacos/imunologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Complicações Cardiovasculares na Gravidez/imunologia , Receptores Adrenérgicos beta 1/imunologia , Animais , Anticorpos/metabolismo , Cardiomiopatias/genética , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Linhagem Celular , Feminino , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Período Periparto , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Gravidez , Complicações Cardiovasculares na Gravidez/genética , Complicações Cardiovasculares na Gravidez/metabolismo , Complicações Cardiovasculares na Gravidez/patologia , Ratos Wistar , Receptores Adrenérgicos beta 1/metabolismo , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
18.
J Immunol ; 205(1): 251-260, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32444389

RESUMO

Over the first days of polymicrobial sepsis, there is robust activation of the innate immune system, causing the appearance of proinflammatory cytokines and chemokines, along with the appearance of extracellular histones, which are highly proinflammatory and prothrombotic. In the current study, we studied different innate immune responses in mice with knockout (KO) of complement protein 6 (C6). Polymorphonuclear neutrophils (PMNs) from these KO mice had defective innate immune responses, including defective expression of surface adhesion molecules, generation of superoxide anion, and appearance of reactive oxygen species and histone release after activation of PMNs, along with defective phagocytosis. In addition, in C6-/- mice, the NLRP3 inflammasome was defective both in PMNs and in macrophages. When these KO mice were subjected to polymicrobial sepsis, their survival was improved, associated with reduced levels in the plasma of proinflammatory cytokines and chemokines and lower levels of histones in plasma. In addition, sepsis-induced cardiac dysfunction was attenuated in these KO mice. In a model of acute lung injury induced by LPS, C6-/- mice showed reduced PMN buildup and less lung epithelial/endothelial cell dysfunction (edema and hemorrhage). These data indicate that C6-/- mice have reduced innate immune responses that result in less organ injury and improved survival after polymicrobial sepsis.


Assuntos
Lesão Pulmonar Aguda/imunologia , Cardiomiopatias/imunologia , Coinfecção/imunologia , Complemento C6/metabolismo , Imunidade Inata , Sepse/imunologia , Lesão Pulmonar Aguda/diagnóstico , Lesão Pulmonar Aguda/patologia , Animais , Cardiomiopatias/diagnóstico , Cardiomiopatias/patologia , Coinfecção/complicações , Coinfecção/diagnóstico , Coinfecção/patologia , Complemento C6/genética , Modelos Animais de Doenças , Humanos , Inflamassomos/imunologia , Inflamassomos/metabolismo , Masculino , Camundongos , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neutrófilos/imunologia , Neutrófilos/metabolismo , Sepse/complicações , Sepse/diagnóstico , Sepse/genética , Índice de Gravidade de Doença
19.
Virchows Arch ; 477(5): 733-738, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32388718

RESUMO

Cardiac amyloidosis is most commonly comprised of either a monoclonal immunoglobulin or transthyretin; however, in practice, detailing of the former beyond light chain restriction is not typically performed. We present briefly the case of an 80-year-old man with concern for cardiac amyloidosis and a subsequent endomyocardial biopsy revealing significant deposition of amorphous Congo red-positive material. By immunofluorescence microscopy, the amyloidogenic material showed positive expression for IgG heavy chain and kappa light chain, with negative staining for IgM and IgA heavy chains and lambda light chain supporting a diagnosis of heavy and light chain (AHL)-type amyloidosis. Immunofluorescence staining for the IgG heavy chain subclasses supported and further classified the patient's AHL-type cardiac amyloidosis as being IgG4/kappa restricted. The presented case is the first to illustrate AHL-type cardiac amyloidosis via sampling of heart tissue.


Assuntos
Cardiomiopatias/imunologia , Imunoglobulina G/análise , Cadeias Pesadas de Imunoglobulinas/análise , Amiloidose de Cadeia Leve de Imunoglobulina/imunologia , Cadeias lambda de Imunoglobulina/análise , Miocárdio/imunologia , Idoso de 80 Anos ou mais , Biomarcadores/análise , Biópsia , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/patologia , Imunofluorescência , Humanos , Imunoglobulina A/análise , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico por imagem , Amiloidose de Cadeia Leve de Imunoglobulina/patologia , Imunoglobulina M/análise , Cadeias kappa de Imunoglobulina/análise , Masculino , Miocárdio/patologia
20.
Front Immunol ; 11: 566, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32411123

RESUMO

Heat shock protein A12B (HSPA12B) is predominately expressed in endothelial cells (ECs) and has been reported to protect against cardiac dysfunction from endotoxemia or myocardial infarction. This study investigated the mechanisms by which endothelial HSPA12B protects polymicrobial sepsis-induced cardiomyopathy. Wild-type (WT) and endothelial HSPA12B knockout (HSPA12B-/-) mice were subjected to polymicrobial sepsis induced by cecal ligation and puncture (CLP). Cecal ligation and puncture sepsis accelerated mortality and caused severe cardiac dysfunction in HSPA12B-/- mice compared with WT septic mice. The levels of adhesion molecules and the infiltrated immune cells in the myocardium of HSPA12B-/- septic mice were markedly greater than in WT septic mice. The levels of microRNA-126 (miR-126), which targets adhesion molecules, in serum exosomes from HSPA12B-/- septic mice were significantly lower than in WT septic mice. Transfection of ECs with adenovirus expressing HSPA12B significantly increased miR-126 levels. Increased miR-126 levels in ECs prevented LPS-stimulated expression of adhesion molecules. In vivo delivery of miR-126 carried by exosomes into the myocardium of HSPA12B-/- mice significantly attenuated CLP sepsis increased levels of adhesion molecules, and improved CLP sepsis-induced cardiac dysfunction. The data suggest that HSPA12B protects against sepsis-induced severe cardiomyopathy via regulating miR-126 expression which targets adhesion molecules, thus decreasing the accumulation of immune cells in the myocardium.


Assuntos
Cardiomiopatias/metabolismo , Células Endoteliais/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , MicroRNAs/metabolismo , Animais , Cardiomiopatias/etiologia , Cardiomiopatias/imunologia , Moléculas de Adesão Celular , Regulação da Expressão Gênica/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Sepse/complicações , Sepse/imunologia , Sepse/metabolismo
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