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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
2.
J Am Heart Assoc ; 10(16): e021428, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34365798

RESUMO

Background Cardiac dysfunction is a prominent feature of multisystem inflammatory syndrome in children (MIS-C), yet the etiology is poorly understood. We determined whether dysfunction is global or regional, and whether it is associated with the cytokine milieu, microangiopathy, or severity of shock. Methods and Results We analyzed echocardiographic parameters of myocardial deformation and compared global and segmental left ventricular strain between 43 cases with MIS-C ≤18 years old and 40 controls. Primary outcomes included left ventricular global longitudinal strain, right ventricular free wall strain), and left atrial strain. We evaluated relationships between strain and profiles of 10 proinflammatory cytokines, microangiopathic features (soluble C5b9), and vasoactive-inotropic requirements. Compared with controls, cases with MIS-C had significant impairments in all parameters of systolic and diastolic function. 65% of cases with MIS-C had abnormal left ventricular function (|global longitudinal strain|<17%), although elevations of cytokines were modest. All left ventricular segments were involved, without apical or basal dominance to suggest acute stress cardiomyopathy. Worse global longitudinal strain correlated with higher ratios of interleukin-6 (ρ -0.43) and interleukin-8 (ρ -0.43) to total hypercytokinemia, but not absolute levels of interleukin-6 or interleukin-8, or total hypercytokinemia. Similarly, worse right ventricular free wall strain correlated with higher relative interleukin-8 expression (ρ -0.59). There were no significant associations between function and microangiopathy or vasoactive-inotropic requirements. Conclusions Myocardial function is globally decreased in MIS-C and not explained by acute stress cardiomyopathy. Cardiac dysfunction may be driven by the relative skew of the immune response toward interleukin-6 and interleukin-8 pathways, more so than degree of hyperinflammation, refining the current paradigm of myocardial involvement in MIS-C.


Assuntos
Função do Átrio Esquerdo , COVID-19/complicações , Síndrome da Liberação de Citocina/etiologia , Citocinas/sangue , Cardiopatias/etiologia , Mediadores da Inflamação/sangue , Síndrome de Resposta Inflamatória Sistêmica/complicações , Função Ventricular Esquerda , Função Ventricular Direita , Adolescente , Fatores Etários , Biomarcadores/sangue , COVID-19/diagnóstico , COVID-19/imunologia , Criança , Estudos Transversais , Síndrome da Liberação de Citocina/diagnóstico , Síndrome da Liberação de Citocina/imunologia , Ecocardiografia , Feminino , Cardiopatias/diagnóstico por imagem , Cardiopatias/imunologia , Cardiopatias/fisiopatologia , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/imunologia
3.
Cardiovasc Pathol ; 54: 107370, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34273507

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is commonly associated with myocardial injury and heart failure. The pathophysiology behind this phenomenon remains unclear, with many diverse and multifaceted hypotheses. To contribute to this understanding, we describe the underlying cardiac findings in fifty patients who died with coronavirus disease 2019 (COVID-19). METHODS: Included were autopsies performed on patients with a positive SARS-CoV-2 reverse-transcriptase-polymerase-chain reaction test from the index hospitalization. In the case of out-of-hospital death, patients were included if post-mortem testing was positive. Complete autopsies were performed according to a COVID-19 safety protocol, and all patients underwent both macroscopic and microscopic examination. If available, laboratory findings and echocardiograms were reported. RESULTS: The median age of the decedents was 63.5 years. The most common comorbidities included hypertension (90.0%), diabetes (56.0%) and obesity (50.0%). Lymphocytic inflammatory infiltrates in the heart were present in eight (16.0%) patients, with focal myocarditis present in two (4.0%) patients. Acute myocardial ischemia was observed in eight (16.0%) patients. The most common findings were myocardial fibrosis (80.0%), hypertrophy (72.0%), and microthrombi (66.0%). The most common causes of death were COVID-19 pneumonia in 18 (36.0%), COVID-19 pneumonia with bacterial superinfection in 12 (24.0%), and COVID-19 pneumonia with pulmonary embolism in 10 (20.0%) patients. CONCLUSIONS: Cardiovascular comorbidities were prevalent, and pathologic changes associated with hypertensive and atherosclerotic cardiovascular disease were the most common findings. Despite markedly elevated inflammatory markers and cardiac enzymes, few patients exhibited inflammatory infiltrates or necrosis within cardiac myocytes. A unifying pathophysiologic mechanism behind myocardial injury in COVID-19 remains elusive, and additional autopsy studies are needed.


Assuntos
COVID-19/patologia , Cardiopatias/patologia , Miocárdio/patologia , SARS-CoV-2/patogenicidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/mortalidade , Aterosclerose/patologia , Autopsia , COVID-19/imunologia , COVID-19/mortalidade , COVID-19/virologia , Comorbidade , Feminino , Cardiopatias/imunologia , Cardiopatias/mortalidade , Cardiopatias/virologia , Interações Hospedeiro-Patógeno , Humanos , Hipertensão/mortalidade , Hipertensão/patologia , Mediadores da Inflamação/análise , Masculino , Pessoa de Meia-Idade , Miocárdio/imunologia , Necrose , SARS-CoV-2/imunologia , Regulação para Cima
5.
Pharmacol Res ; 168: 105581, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33781873

RESUMO

In-depth characterization of heart-brain communication in critically ill patients with severe acute respiratory failure is attracting significant interest in the COronaVIrus Disease 19 (COVID-19) pandemic era during intensive care unit (ICU) stay and after ICU or hospital discharge. Emerging research has provided new insights into pathogenic role of the deregulation of the heart-brain axis (HBA), a bidirectional flow of information, in leading to severe multiorgan disease syndrome (MODS) in patients with confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Noteworthy, HBA dysfunction may worsen the outcome of the COVID-19 patients. In this review, we discuss the critical role HBA plays in both promoting and limiting MODS in COVID-19. We also highlight the role of HBA as new target for novel therapeutic strategies in COVID-19 in order to open new translational frontiers of care. This is a translational perspective from the Italian Society of Cardiovascular Researches.


Assuntos
Encefalopatias/terapia , Encéfalo/efeitos dos fármacos , COVID-19/terapia , Cardiopatias/terapia , Coração/efeitos dos fármacos , Corticosteroides/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Antivirais/administração & dosagem , Encéfalo/imunologia , Encéfalo/metabolismo , Encefalopatias/imunologia , Encefalopatias/metabolismo , COVID-19/imunologia , COVID-19/metabolismo , Cuidados Críticos/métodos , Estado Terminal/terapia , Suplementos Nutricionais , Alimento Funcional , Cardiopatias/imunologia , Cardiopatias/metabolismo , Humanos , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Microvasos/efeitos dos fármacos , Microvasos/imunologia , Microvasos/metabolismo , Insuficiência de Múltiplos Órgãos/imunologia , Insuficiência de Múltiplos Órgãos/metabolismo , Insuficiência de Múltiplos Órgãos/terapia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo
6.
Front Immunol ; 12: 584538, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679735

RESUMO

The cardiovascular and immune systems undergo profound and intertwined alterations with aging. Recent studies have reported that an accumulation of memory and terminally differentiated T cells in elderly subjects can fuel myocardial aging and boost the progression of heart diseases. Nevertheless, it remains unclear whether the immunological senescence profile is sufficient to cause age-related cardiac deterioration or merely acts as an amplifier of previous tissue-intrinsic damage. Herein, we sought to decompose the causality in this cardio-immune crosstalk by studying young mice harboring a senescent-like expanded CD4+ T cell compartment. Thus, immunodeficient NSG-DR1 mice expressing HLA-DRB1*01:01 were transplanted with human CD4+ T cells purified from matching donors that rapidly engrafted and expanded in the recipients without causing xenograft reactions. In the donor subjects, the CD4+ T cell compartment was primarily composed of naïve cells defined as CCR7+CD45RO-. However, when transplanted into young lymphocyte-deficient mice, CD4+ T cells underwent homeostatic expansion, upregulated expression of PD-1 receptor and strongly shifted towards effector/memory (CCR7- CD45RO+) and terminally-differentiated phenotypes (CCR7-CD45RO-), as typically seen in elderly. Differentiated CD4+ T cells also infiltrated the myocardium of recipient mice at comparable levels to what is observed during physiological aging. In addition, young mice harboring an expanded CD4+ T cell compartment showed increased numbers of infiltrating monocytes, macrophages and dendritic cells in the heart. Bulk mRNA sequencing analyses further confirmed that expanding T-cells promote myocardial inflammaging, marked by a distinct age-related transcriptomic signature. Altogether, these data indicate that exaggerated CD4+ T-cell expansion and differentiation, a hallmark of the aging immune system, is sufficient to promote myocardial alterations compatible with inflammaging in juvenile healthy mice.


Assuntos
Envelhecimento/imunologia , Linfócitos T CD4-Positivos/imunologia , Diferenciação Celular/imunologia , Cardiopatias/imunologia , Memória Imunológica/imunologia , Miocárdio/imunologia , Envelhecimento/genética , Animais , Linfócitos T CD4-Positivos/metabolismo , Diferenciação Celular/genética , Células Cultivadas , Expressão Gênica/imunologia , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB1/imunologia , Cadeias HLA-DRB1/metabolismo , Cardiopatias/genética , Cardiopatias/metabolismo , Humanos , Memória Imunológica/genética , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Camundongos Transgênicos , RNA-Seq/métodos , Transplante Heterólogo
7.
Am J Med Sci ; 361(6): 718-724, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33582156

RESUMO

BACKGROUND: Inflammation can facilitate development of coronavirus disease 2019 (COVID-19) and cardiac injury is associated with worse clinical outcomes. However, data are relatively scarce on the association between hyper-inflammatory response and cardiac injury among COVID-19 patients. METHODS: The study was designed based on severe and critically ill patients with COVID-19. Information on clinical characteristics and laboratory examinations was collected from the electronic medical records and analyzed. RESULTS: There were 32.4% (n = 107) of patients with cardiac injury. The median age was 67 years, and 48.8% (n = 161) of patients were men. Hypertension was the most common in 161 (48.8%) patients, followed by diabetes (16.7%, n = 55) and coronary heart disease (13.3%, n = 44). Compared to cases without cardiac injury, those with cardiac injury were older, had higher proportions of coronary heart disease, and leukocyte counts, significantly elevated concentrations of N-terminal pro-B-Type natriuretic peptide, high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-α, interleukin-2 receptor (IL-2R), IL-6, and IL-8, but lower lymphocyte counts. A significant positive correlation was observed between high-sensitivity troponin I and inflammatory cytokines. Logistic regression analysis showed that hs-CRP, TNF-α and IL-6 were independent risk factors for cardiac injury. CONCLUSIONS: Cardiac injury was associated with elevated levels of inflammatory cytokines among severe and critically ill patients with COVID-19, suggesting that hyper-inflammatory response may involve in cardiac injury.


Assuntos
COVID-19 , Cardiopatias , SARS-CoV-2 , Troponina I/sangue , Idoso , Proteína C-Reativa/análise , COVID-19/imunologia , COVID-19/fisiopatologia , COVID-19/terapia , Fatores de Risco Cardiometabólico , China/epidemiologia , Estado Terminal/epidemiologia , Estado Terminal/terapia , Diabetes Mellitus/epidemiologia , Feminino , Cardiopatias/diagnóstico , Cardiopatias/imunologia , Cardiopatias/virologia , Humanos , Hipertensão/epidemiologia , Interleucina-6/sangue , Masculino , Medição de Risco , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/complicações , Síndrome de Resposta Inflamatória Sistêmica/virologia , Fator de Necrose Tumoral alfa/sangue
8.
J Cell Physiol ; 236(6): 4625-4639, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33452697

RESUMO

Sepsis-induced myocardial dysfunction (SIMD), a deadly symptom in sepsis patients, is mainly caused by cardiovascular inflammation. However, it remains unclear how systemic inflammation triggers and aggravates cardiovascular inflammation in the pathogenesis of SIMD. This study found that proinflammatory cytokines and H2 O2 concentrations were significantly induced in SIMD-mice. In particular, a microarray analysis of CD63+ exosomes isolated from sham- and SIMD-monocytes revealed a significant induction of thioredoxin-interacting protein (TXNIP) and NLR family pyrin domain-containing 3 (NLRP3). We proved that oxidative stress caused the disassociation of the TXNIP-TRX2 (thioredoxin 2) complex and the assembly of the TXNIP-NLRP3 complex. In addition, this finding showed that the latter complex could be embedded into CD63+ exosomes and traffic from monocytes to the resident heart macrophages, where it activated caspase-1 and cleaved inactive interleukin 1ß (IL-1ß) and IL-18. Furthermore, using an amplified luminescent proximity homogeneous assay (Alpha) with GST-TXNIP and His-NLRP3, we obtained a small molecule named PSSM1443 that could disrupt the TXNIP-NLRP3 interaction in vitro, impairing NLRP3 downstream events. Of note, after administering PSSM1443 to the SIMD-mice, we found the small molecule could significantly suppress the activation of caspase-1 and the cleavage of pro-IL-1ß and pro-IL-18, reducing inflammation in the SIMD-mice. Collectively, our results reveal that monocyte-derived exosomes harbor the overexpressed TXNIP-NLRP3 complex, which traffics from circulating monocytes to local macrophages and promotes the cleavage of inactive IL-1ß and IL-18 in the macrophages, aggravating cardiovascular inflammation. PSSM1443 functions as an inhibitor of the TXNIP-NLRP3 complex and its administration can decrease inflammation in SIMD-mice.


Assuntos
Anti-Inflamatórios/farmacologia , Proteínas de Transporte/metabolismo , Exossomos/efeitos dos fármacos , Cardiopatias/prevenção & controle , Inflamassomos/metabolismo , Mediadores da Inflamação/metabolismo , Inflamação/prevenção & controle , Macrófagos/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sepse/tratamento farmacológico , Tiorredoxinas/metabolismo , Animais , Proteínas de Transporte/genética , Técnicas de Cocultura , Modelos Animais de Doenças , Exossomos/genética , Exossomos/imunologia , Exossomos/metabolismo , Cardiopatias/etiologia , Cardiopatias/imunologia , Cardiopatias/metabolismo , Inflamassomos/genética , Inflamação/etiologia , Inflamação/imunologia , Inflamação/metabolismo , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/imunologia , Monócitos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Estresse Oxidativo , Células RAW 264.7 , Sepse/complicações , Sepse/imunologia , Sepse/metabolismo , Tetraspanina 30/metabolismo , Tiorredoxinas/genética
9.
J Intern Med ; 289(4): 523-531, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32976665

RESUMO

BACKGROUND: A high proportion of COVID-19 patients have cardiac involvement, even those without known cardiac disease. Downregulation of angiotensin converting enzyme 2 (ACE2), a receptor for SARS-CoV-2 and the renin-angiotensin system, as well as inflammatory mechanisms have been suggested to play a role. ACE2 is abundant in the gut and associated with gut microbiota composition. We hypothesized that gut leakage of microbial products, and subsequent inflammasome activation could contribute to cardiac involvement in COVID-19 patients. METHODS: Plasma levels of a gut leakage marker (LPS-binding protein, LBP), a marker of enterocyte damage (intestinal fatty acid binding protein, IFABP), a gut homing marker (CCL25, ligand for chemokine receptor CCR9) and markers of inflammasome activation (IL-1ß, IL-18 and their regulatory proteins) were measured at three time points (day 1, 3-5 and 7-10) in 39 hospitalized COVID-19 patients and related to cardiac involvement. RESULTS: Compared to controls, COVID-19 patients had elevated plasma levels of LBP and CCL25 but not IFABP, suggesting impaired gut barrier function and accentuated gut homing of T cells without excessive enterocyte damage. Levels of LBP were twice as high at baseline in patients with elevated cardiac markers compared with those without and remained elevated during hospitalization. Also, markers of inflammasome activation were moderately elevated in patients with cardiac involvement. LBP was associated with higher NT-pro-BNP levels, whereas IL-18, IL-18BP and IL-1Ra were associated with higher troponin levels. CONCLUSION: Patients with cardiac involvement had elevated markers of gut leakage and inflammasome activation, suggestive of a potential gut-heart axis in COVID-19.


Assuntos
COVID-19 , Quimiocinas CC/metabolismo , Microbioma Gastrointestinal/imunologia , Cardiopatias , Inflamassomos/metabolismo , Mucosa Intestinal , SARS-CoV-2 , Proteínas de Fase Aguda/metabolismo , COVID-19/complicações , COVID-19/imunologia , Proteínas de Transporte/metabolismo , Correlação de Dados , Cardiopatias/imunologia , Cardiopatias/virologia , Humanos , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/fisiopatologia , Glicoproteínas de Membrana/metabolismo , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , Troponina/sangue
10.
Int J Cardiol ; 326: 237-242, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33098952

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic. The ability to predict cardiac injury and analyze lymphocyte immunity and inflammation of cardiac damage in patients with COVID-19 is limited. We aimed to determine the risk factors and predictive markers of cardiac injury in these patients. METHODS: Data from 124 consecutive hospitalized patients with confirmed COVID-19 were collected. We compared the proportion of cardiovascular disease history in moderate, severe, and critical cases. We obtained high-sensitivity cardiac troponin I (hs-cTn I) results from 68 patients. Patients were divided into two groups based on positive hs-cTn I result: those with cardiac injury (n = 19) and those without cardiac injury (n = 49). RESULTS: Compared with the group with moderate disease, hypertension, coronary heart disease, and smoking were more common in severe and critical cases. Diabetes mellitus was most common in the critical group. Age older than 65 years, presence of chronic kidney disease, and lower blood lymphocyte percentage were independent risk factors of cardiac injury. The total T- and B-lymphocyte counts and CD4+ and CD8+ T-cell counts were significantly lower in those with cardiac injury. A minimal lymphocyte percentage < 7.8% may predict cardiac injury. The interleukin (IL) 6 level in plasma was elevated in the group with cardiac injury. CONCLUSIONS: The lymphocyte percentage in blood may become a predictive marker of cardiac injury in COVID-19 patients. The total T and B cells and CD4+ and CD8+ cell counts decreased and the IL-6 level increased in COVID-19 patients with cardiac injury.


Assuntos
COVID-19/sangue , Cardiopatias/sangue , Hospitalização/tendências , Imunidade Celular/fisiologia , Mediadores da Inflamação/sangue , Linfócitos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , COVID-19/epidemiologia , COVID-19/imunologia , China/epidemiologia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/imunologia , Feminino , Cardiopatias/epidemiologia , Cardiopatias/imunologia , Humanos , Mediadores da Inflamação/imunologia , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/imunologia , Estudos Retrospectivos
11.
Medicine (Baltimore) ; 99(51): e23773, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33371145

RESUMO

ABSTRACT: Chagas disease affects approximately 7 million people, causing disability and mortality in the most productive life stages of infected individuals. Considering the lifestyle of the world population, metabolic syndrome is a synergistic factor for an increased cardiovascular risk of patients with Chagas disease.This study transversally evaluated the metabolic and immunological profiles of patients with indeterminate (IF) and cardiac (CF) forms of Chagas disease and their correlations with left ventricular dysfunction (LVD).Clinical and electrical bioimpedance analysis, levels of cytokines (interferon [IFN]-γ, tumor necrosis factor [TNF]-α, interleukin [IL]-17, IL-10, and IL-33) and adipocytokines (adiponectin, leptin, and resistin), metabolic syndrome components, and brain natriuretic peptide (BNP) levels were assessed in 57 patients (13 IF and 44 CF) with a mean age of 61.63 ±â€Š12.1 years. Chest x-ray, electrocardiogram, and echocardiogram were performed to classify the clinical forms.The CF group had a higher number of individuals with metabolic syndrome components blood pressure altered, while more participants in the CF group with LVD had low high-density lipoprotein (HDL) levels. The IF group had more participants with a higher waist-to-hip ratio (WHR). No significant difference was observed between metabolic syndrome, cytokine and adipocytokine level, and clinical forms of the disease or in relation to LVD.Individuals with the IF showed metabolic and immunological profiles compatible with increased disease control, whereas those with CF showed marked inflammatory immune response.


Assuntos
Doença de Chagas/imunologia , Doença de Chagas/metabolismo , Adiponectina/análise , Adiponectina/sangue , Idoso , Análise de Variância , Biomarcadores/análise , Biomarcadores/sangue , Feminino , Cardiopatias/imunologia , Cardiopatias/metabolismo , Humanos , Interleucina-10/análise , Interleucina-10/sangue , Interleucina-17/análise , Interleucina-17/biossíntese , Interleucina-33/análise , Interleucina-33/sangue , Leptina/análise , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Resistina/análise , Resistina/sangue , Estatísticas não Paramétricas
12.
Trends Endocrinol Metab ; 31(12): 893-904, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33172748

RESUMO

Coronavirus disease 2019 (COVID-19) patients with pre-existing cardiovascular disease (CVD) or with cardiovascular complications have a higher risk of mortality. The main cardiovascular complications of COVID-19 include acute cardiac injury, acute myocardial infarction (AMI), myocarditis, arrhythmia, heart failure, shock, and venous thromboembolism (VTE)/pulmonary embolism (PE). COVID-19 can cause cardiovascular complications or deterioration of coexisting CVD through direct or indirect mechanisms, including viral toxicity, dysregulation of the renin-angiotensin-aldosterone system (RAAS), endothelial cell damage and thromboinflammation, cytokine storm, and oxygen supply-demand mismatch. We systematically review cardiovascular manifestations, histopathology, and mechanisms of COVID-19, to help to formulate future research goals and facilitate the development of therapeutic management strategies.


Assuntos
COVID-19/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , Enzima de Conversão de Angiotensina 2/metabolismo , Arritmias Cardíacas/imunologia , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , COVID-19/imunologia , COVID-19/metabolismo , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/metabolismo , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/fisiopatologia , Cardiopatias/imunologia , Cardiopatias/metabolismo , Cardiopatias/fisiopatologia , Insuficiência Cardíaca/imunologia , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipóxia/imunologia , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Infarto do Miocárdio/imunologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Miocardite/imunologia , Miocardite/metabolismo , Miocardite/fisiopatologia , Embolia Pulmonar/imunologia , Embolia Pulmonar/metabolismo , Embolia Pulmonar/fisiopatologia , Sistema Renina-Angiotensina/fisiologia , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , Choque/imunologia , Choque/metabolismo , Choque/fisiopatologia , Troponina/metabolismo , Tromboembolia Venosa/imunologia , Tromboembolia Venosa/metabolismo , Tromboembolia Venosa/fisiopatologia
13.
Curr Cardiol Rep ; 22(5): 32, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32318865

RESUMO

PURPOSE OF REVIEW: Coronavirus disease of 2019 (COVID-19) is a cause of significant morbidity and mortality worldwide. While cardiac injury has been demonstrated in critically ill COVID-19 patients, the mechanism of injury remains unclear. Here, we review our current knowledge of the biology of SARS-CoV-2 and the potential mechanisms of myocardial injury due to viral toxicities and host immune responses. RECENT FINDINGS: A number of studies have reported an epidemiological association between history of cardiac disease and worsened outcome during COVID infection. Development of new onset myocardial injury during COVID-19 also increases mortality. While limited data exist, potential mechanisms of cardiac injury include direct viral entry through the angiotensin-converting enzyme 2 (ACE2) receptor and toxicity in host cells, hypoxia-related myocyte injury, and immune-mediated cytokine release syndrome. Potential treatments for reducing viral infection and excessive immune responses are also discussed. COVID patients with cardiac disease history or acquire new cardiac injury are at an increased risk for in-hospital morbidity and mortality. More studies are needed to address the mechanism of cardiotoxicity and the treatments that can minimize permanent damage to the cardiovascular system.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Cardiopatias/complicações , Cardiopatias/imunologia , Cardiopatias/virologia , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Enzima de Conversão de Angiotensina 2 , Animais , Betacoronavirus , COVID-19 , Infecções por Coronavirus/terapia , Citocinas/imunologia , Humanos , Hipóxia/patologia , Miócitos Cardíacos/patologia , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/terapia , SARS-CoV-2
15.
Prog Cardiovasc Dis ; 63(3): 194-209, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32205133

RESUMO

Cardiac allograft vasculopathy (CAV)-mediated by a heterogeneous myriad of immune and non-immune factors, which contribute to the progressive and diffuse thickening of the arterial allograft's tunica intima in one distinct form of CAV, and the build-up of plaque in another-is a major limiting factor of long-term survival post heart transplantation. Information on the optimal pharmacotherapeutic approaches for the prevention and management of CAV is conflicting, scattered, and inconsistent, with numerous recent studies adding to the literature. In this paper, we present a go-to clinical resource with the most updated and comprehensive information on the topic. Immunosuppressant therapy remains a staple, with mTOR inhibitors and mycophenolate mofetil (MMF) showing direct correlation with CAV prevention. More data is now available with calcineurin inhibitor (CNI) minimizing or sparing regimens. More novel approaches are being investigated for the roles of monoclonal antibodies, anti-thymocyte globulin, and bortezomib in preventing or delaying CAV. On the other hand, statins' established efficacy is attributed to lipid-lowering and lipid-independent immunomodulatory effects, with early initiation associated with improved outcomes. The choice of statin is dependent on drug-drug interactions. Other aiding approaches for the prevention of CAV include antioxidant vitamins, aspirin, vasodilators, folate therapy, and, most pertinently, cytomegalovirus prophylaxis. Larger clinical trials are needed before these options are institutionalised. For management of established CAV, early initiation of augmented immunosuppressive therapies may be effective, as well as CNI conversion to mTOR inhibitors with or without standard MMF and azathioprine therapy. Risk of acute rejection needs to be monitored during conversion. Finally, preclinical investigations highlight novel potential therapies for CAV prevention and attenuation, however robust clinical trials are needed to test their efficacy and safety.


Assuntos
Cardiopatias/prevenção & controle , Transplante de Coração/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Imunossupressores/uso terapêutico , Animais , Cardiopatias/epidemiologia , Cardiopatias/imunologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Imunossupressores/efeitos adversos , Fatores de Risco , Resultado do Tratamento
16.
Toxicology ; 435: 152410, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32068018

RESUMO

Epidemiologic studies show that the levels of air pollutants and particulate matter are positively associated with the morbidity and mortality of cardiovascular diseases. Here we demonstrate that the intratracheal instillation of multi-walled carbon nanotubes (MWCNTs), a standard fine particle, exacerbate doxorubicin (DOX)-induced cardiotoxicity in mice through altering gut microbiota and pulmonary and colonic macrophage phenotype. MWCNTs (25 µg/kg per day, 5 days a week for 3 weeks) promoted cardiotoxicity and apoptosis in the DOX (2 mg/kg, twice a week for 5 weeks)-treated C57BL/6 mice. MWCNTs exaggerated DOX-induced gut microbiota dysbiosis characterized by the increased abundances of Helicobacteraceae and Coriobacteriaceae. In addition, MWCNTs promoted DOX-induced M1-like polarization of colonic macrophages with an increase in TNF-α, IL-1ß and CC chemokine ligand 2 in peripheral blood. Importantly, treatment with the antibiotics attenuated MWCNTs plus DOX-induced apoptosis of cardiomyocytes and M1-like polarization of colonic macrophages. The fecal microbiota transplantation demonstrated that MWCNTs exaggerated DOX-induced cardiotoxicity with M1-like polarization of colonic macrophages. The conditioned medium from MWCNTs-treated pulmonary macrophages promoted DOX-induced gut microbiota dysbiosis and colonic macrophage polarization. Furthermore, the co-culture of macrophages and fecal bacteria promoted M1-like macrophage polarization and their production of TNF-α and IL-1ß, and thereby exacerbated the effects of MWCNTs. Moreover, IL-1ß and TNF-α blockade, either alone or in combination attenuated MWCNTs-exacerbated cardiotoxicity. In summary, MWCNTs exacerbate DOX-induced cardiotoxicity in mice through gut microbiota and pulmonary and colonic macrophage interaction. Our findings identify a novel mechanism of action of inhaled particle-driven cardiotoxicity.


Assuntos
Antibióticos Antineoplásicos/toxicidade , Colo/efeitos dos fármacos , Doxorrubicina/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Cardiopatias/induzido quimicamente , Pulmão/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Nanotubos de Carbono/toxicidade , Animais , Antibacterianos/farmacologia , Apoptose/efeitos dos fármacos , Células Cultivadas , Quimiocina CCL2/sangue , Colo/imunologia , Colo/metabolismo , Colo/microbiologia , Disbiose , Fezes/microbiologia , Cardiopatias/sangue , Cardiopatias/imunologia , Cardiopatias/microbiologia , Interleucina-1beta/sangue , Pulmão/imunologia , Pulmão/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fenótipo , Fator de Necrose Tumoral alfa/sangue
17.
PLoS One ; 15(1): e0227449, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32004354

RESUMO

The SOD3 variant, SOD3R213G, results from substitution of arginine to glycine at amino acid 213 (R213G) in its heparin binding domain (HBD) and is a common genetic variant, reported to be associated with ischemic heart disease. However, little is understood about the role of SOD3R213G in innate immune function, and how it leads to dysfunction of the cardiovascular system. We observed pathologic changes in SOD3R213G transgenic (Tg) mice, including cystic medial degeneration of the aorta, heart inflammation, and increased circulating and organ infiltrating neutrophils. Interestingly, SOD3R213G altered the profile of SOD3 interacting proteins in neutrophils in response to G-CSF. Unexpectedly, we found that G-CSF mediated tyrosine phosphatase, SH-PTP1 was down-regulated in the neutrophils of SOD3R213G overexpressing mice. These effects were recovered by reconstitution with Wt SOD3 expressing bone marrow cells. Overall, our study reveals that SOD3R213G plays a crucial role in the function of the cardiovascular system by controlling innate immune response and signaling. These results suggest that reconstitution with SOD3 expressing bone marrow cells may be a therapeutic strategy to treat SOD3R213G mediated diseases.


Assuntos
Infiltração de Neutrófilos/fisiologia , Neutrófilos/metabolismo , Superóxido Dismutase/metabolismo , Animais , Aorta/metabolismo , Aorta/patologia , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Proliferação de Células , Modelos Animais de Doenças , Regulação para Baixo , Fator Estimulador de Colônias de Granulócitos/metabolismo , Cardiopatias/imunologia , Cardiopatias/metabolismo , Cardiopatias/patologia , Imunidade Inata , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutagênese Sítio-Dirigida , Miocárdio/metabolismo , Miocárdio/patologia , Neutrófilos/citologia , Proteína Tirosina Fosfatase não Receptora Tipo 6/metabolismo , Receptores CCR2/metabolismo , Transdução de Sinais , Superóxido Dismutase/genética
18.
Basic Res Cardiol ; 115(2): 8, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31897858

RESUMO

Macrophages are one cell type in the innate immune system. Recent studies involving macrophages have overturned the conventional concept that circulating bone marrow-derived blood mononuclear cells in the adult body continuously replace macrophages residing in the tissues. Investigations using refined technologies have suggested that embryonic hematopoiesis can result in the differentiation into macrophage subgroups in some tissues. In adulthood, these macrophages are self-sustaining via in situ proliferation, with little contribution of circulating bone marrow-derived blood mononuclear cells. Macrophages are integral component of the heart, accounting for 8% of the non-cardiac cells. The use of innovative molecular techniques in paradigm shifting researches has revealed the complexity of cardiac macrophages, including their heterogeneity and ontological diversity. Resident cardiac macrophages modulate the physiological and pathophysiological processes of the cardiovascular system, with distinct and crucial roles in healthy and injured hearts. Their functions include sensing of pathogens, antigen presentation, digesting cell debris, regulating inflammatory responses, generating distinct cytokines, and secreting some regulatory factors. More recent studies have revealed further functions of cardiac macrophages. This review focuses on macrophages within the cardiovascular system. We discuss evidence that has changed our collective view of cardiac macrophage subgroups, and improved our understanding of the different phenotypes, cell surface markers, heterogeneities, origins, developments, and the dynamic and separate roles of these cardiac macrophage subgroups in the steady state and injured hearts. This review may provide novel insights concerning the pathophysiology of cardiac-resident macrophages in cardiovascular diseases and innovative therapeutic strategies that could include the modulation of the role of macrophages in cardiovascular injuries.


Assuntos
Cardiopatias/imunologia , Imunidade Inata , Macrófagos/imunologia , Miocárdio/imunologia , Animais , Diferenciação Celular , Linhagem da Célula , Proliferação de Células , Cardiopatias/metabolismo , Cardiopatias/patologia , Humanos , Macrófagos/metabolismo , Macrófagos/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Fenótipo , Transdução de Sinais
19.
Transfus Clin Biol ; 27(1): 25-29, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31708346

RESUMO

OBJECTIVES: Red blood cell autoantibodies (RBC autoAbs) of IgG class are found in the majority of patients with warm autoimmune hemolytic anemia (wAIHA) but sometimes also during the pretransfusion testing of patients with different diagnoses but without hemolysis. The aim of the study was to identify the main differences between these two groups of patients according to age, gender, subclass and titer of IgG RBC autoAbs and diagnosis. MATERIAL AND METHODS: In the 9-year retrospective study, data were collected from records of 291 patients with IgG RBC autoAbs detected by gel technique, from which 111 with wAIHA. RESULTS: More than 85% of patients in both groups were over 40 years old, with male to female ratio 1:1.9 in wAIHA vs 1:1.3 in patients without hemolysis (P=0.0916). The main characteristics of patients with wAIHA vs patients without hemolysis were: IgG only 38% vs 70%, IgG+Complement 62% vs 30%, total IgG1 79% vs 55%, IgG1+IgG3 35% vs 11%, titer of 100 for IgG1+IgG3 17% vs 3% (P<0.0001), respectively, while titer of 100 for IgG1 18% vs 9% (P=0.0241). The underlying diagnosis in wAIHA vs patients without hemolysis: hematologic disorders 41% vs 22% (P=0.0006), autoimmune disorders 12% vs 13% (P=0.8033), solid tumors 5% vs 14% (P=0.0154) and surgery procedures 6% vs 26% (P<0.0001). CONCLUSION: We observed more wAIHA patients with high titer of IgG1 and high prevalence of IgG1+IgG3 and consider that patients without hemolysis having identical results might be interesting to find out how they are protected from damage by RBC autoAbs.


Assuntos
Anemia Hemolítica Autoimune/imunologia , Autoanticorpos/sangue , Eritrócitos/imunologia , Imunoglobulina G/sangue , Idoso , Anemia Hemolítica Autoimune/sangue , Anemia Hemolítica Autoimune/etiologia , Grupos Diagnósticos Relacionados , Feminino , Cardiopatias/sangue , Cardiopatias/imunologia , Hemólise , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/imunologia , Hepatopatias/sangue , Hepatopatias/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/imunologia , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/imunologia , Estudos Retrospectivos
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