Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 9.565
Filtrar
1.
Cancer Med ; 13(10): e7233, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38752474

RESUMO

BACKGROUND: Over the past decade, immune checkpoint inhibitors (ICIs) have significantly transformed cancer treatment. However, ICIs inevitably may cause a spectrum of immune-related adverse events, among which cardiovascular toxicity, particularly myocarditis, while infrequent, has garnered increasing attention due to its high fatality rate. METHODS: We conducted a multicenter retrospective study to characterize ICI-associated cardiovascular adverse events. Logistic regression was performed to explore the risk factors for the development of myocarditis and severe myocarditis. Receiver operating characteristic curves were conducted to assess the diagnostic abilities of cardiac biomarkers to distinguish different cardiovascular toxicities, and the performance and calibration were evaluated using Hosmer-Lemeshow test. RESULTS: Forty-four patients were identified, including thirty-five myocarditis, five heart failure, three arrhythmias, and one myocardial infarction. Compared with other patients, myocarditis patients had higher cardiac troponin-I (cTnI) levels (p < 0.001), higher creatine kinase levels (p = 0.003), higher creatine kinase isoenzyme-MB (CK-MB) levels (p = 0.013), and shorter time to the incidence of adverse cardiovascular events (p = 0.022) after ICI treatment. Twenty-one patients (60%) were classified as severe myocarditis, and they presented higher cardiac troponin I (cTnI) levels (p = 0.013), higher N-terminal pro-B-type natriuretic peptide levels (p = 0.031), higher creatine kinase levels (p = 0.018), higher CK-MB levels (p = 0.026), and higher neutrophil to lymphocyte ratio (NLR) levels (p = 0.016) compared to non-severe myocarditis patients after ICI treatment. Multivariate logistic regression showed that CK-MB (adjusted odds ratio [OR]: 1.775, 95% confidence interval [CI]: 1.055-2.984, p = 0.031) was the independent risk factor of the development of ICI-associated myocarditis, and cTnI (adjusted OR: 1.021, 95% CI: 1.002-1.039, p = 0.03) and NLR (adjusted OR: 1.890, 95% CI: 1.026-3.483, p = 0.041) were the independent risk factors of ICI-associated severe myocarditis. The receiver operating characteristic curve showed an area under curve of 0.785 (95% CI: 0.642 to 0.928, p = 0.013) for CK-MB, 0.765 (95% CI: 0.601 to 0.929, p = 0.013) for cTnI, and 0.773 for NLR (95% CI: 0.597 to 0.948, p = 0.016). CONCLUSIONS: Elevated CK-MB after ICI treatment is the independent risk factor for the incidence of ICI-associated myocarditis, and elevated cTnI and NLR after ICI treatment are the independent risk factors for the development of ICI-associated severe myocarditis. CK-MB, cTnI, and NLR demonstrated a promising predictive utility for the identification of ICI-associated myocarditis and severe myocarditis.


Assuntos
Inibidores de Checkpoint Imunológico , Miocardite , Humanos , Masculino , Estudos Retrospectivos , Feminino , Inibidores de Checkpoint Imunológico/efeitos adversos , Miocardite/induzido quimicamente , Miocardite/epidemiologia , Miocardite/diagnóstico , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Biomarcadores/sangue , Neoplasias/tratamento farmacológico , Troponina I/sangue , Curva ROC , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Creatina Quinase Forma MB/sangue , Peptídeo Natriurético Encefálico/sangue , Insuficiência Cardíaca/induzido quimicamente
2.
Scand J Med Sci Sports ; 34(5): e14667, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38773919

RESUMO

The relationship between exercise-induced troponin elevation and non-obstructive coronary artery disease (CAD) is unclear. This observational study assessed non-obstructive CAD's impact on exercise-induced cardiac Troponin I (cTnI) elevation in middle-aged recreational athletes. cTnI levels of 40 well-trained recreational athletes (73% males, 50 ± 9 years old) were assessed by a high-sensitive cTnI assay 24 h before, and at 3 and 24 h following two high-intensity exercises of different durations; a cardiopulmonary exercise test (CPET), and a 91-km mountain bike race. Workload was measured with power meters. Coronary computed tomography angiography was used to determine the presence or absence of non-obstructive (<50% obstruction) CAD. A total of 15 individuals had non-obstructive CAD (Atherosclerotic group), whereas 25 had no atherosclerosis (normal). There were higher post-exercise cTnI levels following the race compared with CPET, both at 3 h (77.0 (35.3-112.4) ng/L vs. 11.6 (6.4-22.5) ng/L, p < 0.001) and at 24 h (14.7 (6.7-16.3) vs. 5.0 (2.6-8.9) ng/L, p < 0.001). Absolute cTnI values did not differ among groups. Still, the association of cTnI response to power output was significantly stronger in the CAD versus Normal group both at 3 h post-exercise (Rho = 0.80, p < 0.001 vs. Rho = -0.20, p = 0.33) and 24-h post-exercise (Rho = 0.87, p < 0.001 vs. Rho = -0.13, p = 0.55). Exercise-induced cTnI elevation was strongly correlated with exercise workload in middle-aged athletes with non-obstructive CAD but not in individuals without CAD. This finding suggests that CAD influences the relationship between exercise workload and the cTnI response even without coronary artery obstruction.


Assuntos
Doença da Artéria Coronariana , Teste de Esforço , Exercício Físico , Troponina I , Humanos , Masculino , Pessoa de Meia-Idade , Doença da Artéria Coronariana/sangue , Feminino , Troponina I/sangue , Exercício Físico/fisiologia , Adulto , Ciclismo/fisiologia , Carga de Trabalho , Angiografia por Tomografia Computadorizada , Atletas , Angiografia Coronária
3.
Cytokine ; 179: 156620, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38701735

RESUMO

PURPOSE: The emergence of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, but these drugs can also cause severe immune-related adverse effects (irAEs), including myocarditis. Researchers have become interested in exploring ways to mitigate this side effect, and one promising avenue is the use of baricitinib, a Janus kinase inhibitor known to have anti-inflammatory properties. This study aimed to examine the potential mechanism by which baricitinib in ICIs-related myocarditis. METHODS: To establish an ICIs-related myocarditis model, BALB/c mice were administered murine cardiac troponin I (cTnI) peptide and anti-mouse programmed death 1 (PD-1) antibodies. Subsequently, baricitinib was administered to the mice via intragastric administration. Echocardiography, HE staining, and Masson staining were performed to evaluate myocardial functions, inflammation, and fibrosis. Immunofluorescence was used to detect macrophages in the cardiac tissue of the mice.In vitro experiments utilized raw264.7 cells to induce macrophage polarization using anti-PD-1 antibodies. Different concentrations of baricitinib were applied to assess cell viability, and the release of pro-inflammatory cytokines was measured. The activation of the JAK1/STAT3 signaling pathway was evaluated through western blot analysis. RESULTS: Baricitinib demonstrated its ability to improve cardiac function and reduce cardiac inflammation, as well as fibrosis induced by ICIs. Mechanistically, baricitinib treatment promoted the polarization of macrophages towards the M2 phenotype. In vitro and in vivo experiments showed that anti-PD-1 promoted the release of inflammatory factors. However, treatment with baricitinib significantly inhibited the phosphorylation of JAK1 and STAT3. Additionally, the use of RO8191 reversed the effects of baricitinib, further confirming our findings. CONCLUSION: Baricitinib demonstrated its potential as a protective agent against ICIs-related myocarditis by modulating macrophage polarization. These findings provide a solid theoretical foundation for the development of future treatments for ICIs-related myocarditis.


Assuntos
Azetidinas , Janus Quinase 1 , Macrófagos , Camundongos Endogâmicos BALB C , Miocardite , Purinas , Pirazóis , Fator de Transcrição STAT3 , Sulfonamidas , Animais , Azetidinas/farmacologia , Miocardite/induzido quimicamente , Miocardite/tratamento farmacológico , Miocardite/patologia , Miocardite/metabolismo , Camundongos , Janus Quinase 1/metabolismo , Sulfonamidas/farmacologia , Fator de Transcrição STAT3/metabolismo , Pirazóis/farmacologia , Purinas/farmacologia , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Células RAW 264.7 , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Masculino , Transdução de Sinais/efeitos dos fármacos , Ativação de Macrófagos/efeitos dos fármacos , Troponina I/metabolismo
4.
Am J Case Rep ; 25: e943645, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38711258

RESUMO

BACKGROUND Neurogenic pulmonary edema (NPE) is a rare complication of neurological insults, such as traumatic brain injury and intracranial hemorrhage, in children. NPE frequently accompanies left ventricular (LV) dysfunction mediated via central catecholamine surge and inflammation. A high serum natriuretic (BNP) level was prolonged even after the LV contraction was improved in this case with severe myocardial injury. The overloading stress to the LV wall can last several days over the acute phase of NPE. CASE REPORT A 6-year-old boy developed NPE after the removal of a brain tumor in the cerebellar vermis, which was complicated by hydrocephalus. Simultaneously, he experienced LV dysfunction involving reduced global contraction with severe myocardial injury diagnosed by abnormally elevated cardiac troponin I level (1611.6 pg/ml) combined with a high serum BNP level (2106 pg/ml). He received mechanical ventilation for 4 days until the improvement of his pulmonary edema in the Intensive Care Unit (ICU). On the next day, after the withdrawal of mechanical ventilation, he was discharged from the ICU to the pediatric unit. Although the LV contraction was restored to an almost normal range in the early period, it took a total of 16 days for the serum BNP level to reach an approximate standard range (36.9 pg/ml). CONCLUSIONS Even in a pediatric patient with NPE, we recommend careful monitoring of the variation of cardiac biomarkers such as BNP until confirmation of return to an approximate normal value because of the possible sustained overloading stress to the LV wall.


Assuntos
Edema Pulmonar , Humanos , Masculino , Edema Pulmonar/etiologia , Criança , Disfunção Ventricular Esquerda/etiologia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/cirurgia , Troponina I/sangue , Complicações Pós-Operatórias , Peptídeo Natriurético Encefálico/sangue
5.
Int J Mol Sci ; 25(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38731803

RESUMO

This study explores the effects of normobaric hypoxia and intermittent hypoxic training (IHT) on the physiological condition of the cardiac muscle in swimmers. Hypoxia has been reported to elicit both beneficial and adverse changes in the cardiovascular system, but its impact on the myocardium during acute exercise and altitude/hypoxic training remains less understood. We aimed to determine how a single bout of intense interval exercise and a four-week period of high-intensity endurance training under normobaric hypoxia affect cardiac marker activity in swimmers. Sixteen young male swimmers were divided into two groups: one undergoing training in hypoxia and the other in normoxia. Cardiac markers, including troponin I and T (cTnI and cTnT), heart-type fatty acid-binding protein (H-FABP), creatine kinase-MB isoenzyme (CK-MB), and myoglobin (Mb), were analyzed to assess the myocardium's response. We found no significant differences in the physiological response of the cardiac muscle to intense physical exertion between hypoxia and normoxia. Four weeks of IHT did not alter the resting levels of cTnT, cTnI, and H-FABP, but it resulted in a noteworthy decrease in the resting concentration of CK-MB, suggesting enhanced cardiac muscle adaptation to exercise. In contrast, a reduction in resting Mb levels was observed in the control group training in normoxia. These findings suggest that IHT at moderate altitudes does not adversely affect cardiac muscle condition and may support cardiac muscle adaptation, affirming the safety and efficacy of IHT as a training method for athletes.


Assuntos
Atletas , Biomarcadores , Hipóxia , Humanos , Masculino , Hipóxia/metabolismo , Projetos Piloto , Natação/fisiologia , Adulto Jovem , Miocárdio/metabolismo , Mioglobina/metabolismo , Troponina I/metabolismo , Proteína 3 Ligante de Ácido Graxo/metabolismo , Adolescente , Proteínas de Ligação a Ácido Graxo/metabolismo , Resistência Física/fisiologia , Creatina Quinase Forma MB/sangue , Creatina Quinase Forma MB/metabolismo , Adaptação Fisiológica , Altitude
6.
Sci Rep ; 14(1): 11488, 2024 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769120

RESUMO

Patients on haemodialysis (HD) have high mortality risk, and prognostic values of the major cardiovascular biomarkers cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), and adiponectin should be ascertained over longer follow-up periods using higher-sensitivity assays, which we undertook. In 221 HD patients, levels of high-sensitivity (hs)-cTnI, NT-proBNP, and adiponectin, were measured using high-sensitivity assays, and their associations with all-cause mortality (ACM) and cardiovascular mortality (CVM) were prospectively investigated for 7 years. Higher hs-cTnI and NT-proBNP levels were significant risk factors for ACM and CVM in the Kaplan-Meier analysis. Multivariate Cox proportional hazards analyses in a model including hs-cTnI and NT-proBNP identified log hs-cTnI, but not log NT-proBNP, as an independent risk factor for ACM (HR 2.12, P < 0.02) and CVM (HR 4.48, P < 0.0005). Stepwise analyses identified a high hs-cTnI tertile as a risk factor for ACM (HR 2.31, P < 0.01) and CVM (HR 6.70, P < 0.001). The addition of hs-cTnI to a model including age, CRP, DM, and NT-proBNP significantly improved the discrimination of ACM and CVM each over 7 years. Conclusively, hs-cTnI was superior to NT-proBNP and adiponectin in predicting ACM and CVM over 7 years in HD patients, suggesting the significance of baseline hs-cTnI measurements in long-term management.


Assuntos
Adiponectina , Biomarcadores , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Diálise Renal , Troponina I , Humanos , Adiponectina/sangue , Troponina I/sangue , Peptídeo Natriurético Encefálico/sangue , Diálise Renal/mortalidade , Masculino , Feminino , Fragmentos de Peptídeos/sangue , Idoso , Pessoa de Meia-Idade , Biomarcadores/sangue , Fatores de Risco , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/sangue , Prognóstico , Estudos Prospectivos , Estimativa de Kaplan-Meier , Modelos de Riscos Proporcionais
7.
Arq Bras Cardiol ; 121(4): e20230544, 2024.
Artigo em Português, Inglês | MEDLINE | ID: mdl-38695471

RESUMO

BACKGROUND: Ablation Index (AI) software has allowed better atrial fibrillation (AF) ablation results, but recurrence rates remain significant. Specific serum biomarkers have been associated with this recurrence. OBJECTIVES: To evaluate whether certain biomarkers could be used (either individually or combined) to predict arrhythmia recurrence after AI-guided AF ablation. METHODS: Prospective multicenter observational study of consecutive patients referred for AF ablation from January 2018 to March 2021. Hemoglobin, brain natriuretic peptide (BNP), C-reactive protein, high sensitivity cardiac troponin I, creatinine clearance, thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were assessed for their ability to predict arrhythmia recurrence during follow-up. Statistical significance was accepted for p values of<0.05. RESULTS: A total of 593 patients were included - 412 patients with paroxysmal AF and 181 with persistent AF. After a mean follow-up of 24±6 months, overall single-procedure freedom from atrial arrhythmia was 76.4%. Individually, all biomarkers had no or only modest predictive power for recurrence. However, a TSH value >1.8 µUI/mL (HR=1.82 [95% CI, 1.89-2.80], p=0.006) was an independent predictor of arrhythmia recurrence. When assessing TSH, FT4 and BNP values in combination, each additional "abnormal" biomarker value was associated with a lower freedom from arrhythmia recurrence (87.1 % for no biomarker vs. 83.5% for one vs. 75.1% for two vs. 43.3% for three biomarkers, p<0.001). Patients with three "abnormal" biomarkers had a threefold higher risk of AF recurrence compared with no "abnormal" biomarker (HR=2.88 [95% CI, 1.39-5.17], p=0.003). CONCLUSIONS: When used in combination, abnormal TSH, FT4 and BNP values can be a useful tool for predicting arrhythmia recurrence after AI-guided AF ablation.


FUNDAMENTO: O software ablation index (AI) permitiu melhorar os resultados da ablação de fibrilação atrial (FA), mas as taxas de recorrência permanecem significativas. Biomarcadores séricos específicos têm sido associados a essa recorrência. OBJETIVOS: Avaliar se certos biomarcadores podem ser utilizados (individualmente ou combinados) para predizer a recorrência de FA pós ablação guiada pelo AI. MÉTODOS: Estudo multicêntrico, observacional, prospectivo de pacientes consecutivos, encaminhados para ablação de FA de janeiro de 2018 a março de 2021. Hemoglobina, peptídeo natriurético cerebral (BNP), proteína C reativa, troponina I ultrassensível, clearance de creatinina, Hormônio Tireoestimulante (TSH), e Tiroxina livre (T4) foram avaliados quanto à capacidade de prever a recorrência de arritmias durante o acompanhamento. Valores de p <0,05 foram aceitos como estatisticamente significativos. RESULTADOS: Um total de 593 pacientes foram incluídos ­ 412 com FA paroxística e 181 com FA persistente. Durante o seguimento médio de 24±6 meses, 76,4% não apresentaram recidiva após ablação. Individualmente, os biomarcadores demonstraram um valor preditivo baixo ou nulo para recorrência. No entanto, TSH >1,8 µUI/mL [HR=1,82 (IC95%, 1,89-2,80), p=0,006] foi um preditor independente de recorrência. Avaliando-se a combinação de TSH, FT4 e BNP, a adição de cada valor "anormal" foi associada a uma menor sobrevida livre de recorrência (87,1% se nenhum vs. 83,5% se um vs. 75,1% se dois vs. 43,3% se três biomarcadores, p<0,001). Doentes com três biomarcadores "anormais" apresentaram três vezes maior probabilidade de recorrência de FA, comparativamente aos que não apresentaram nenhum biomarcador "anormal" (HR=2,88 [IC95%, 1,39-5,17], p=0,003). CONCLUSÕES: Quando combinados, valores anormais de TSH, FT4 e BNP podem ser uma ferramenta útil para prever a recorrência de FA pós ablação guiada pelo AI.


Assuntos
Fibrilação Atrial , Biomarcadores , Ablação por Cateter , Recidiva , Tireotropina , Humanos , Fibrilação Atrial/cirurgia , Fibrilação Atrial/sangue , Biomarcadores/sangue , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Ablação por Cateter/métodos , Idoso , Tireotropina/sangue , Peptídeo Natriurético Encefálico/sangue , Valor Preditivo dos Testes , Proteína C-Reativa/análise , Resultado do Tratamento , Tiroxina/sangue , Fatores de Risco , Troponina I/sangue
8.
PLoS One ; 19(5): e0302984, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38753890

RESUMO

BACKGROUND: Lipoproteins in cell membranes are related to membrane stability and play a role against microorganisms. Patients with COVID-19 often experience myocyte membrane damage. OBJECTIVE: This study aimed to search the relationship of atherogenic indices with myocardial damage and mortality in COVID-19. METHODS: This was an observational, single-center, retrospective study. The study population was grouped according to in-hospital mortality. C-reactive protein (CRP), CRP to albumin ratio (CAR), monocyte to high density lipoprotein cholesterol ratio (MHR), levels of total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDLc), and low-density lipoprotein cholesterol (LDLc) and cardiac troponin I (cTnI) were recorded. Atherogenic indices (plasma atherogenic index [AIP], atherogenic coefficient [AC], Castelli's risk indices I and II [CRI I and II], triglyceride to HDLc ratio (THR) were calculated. RESULTS: A total of 783 patients were included. The mortality rate was 15.45% (n = 121). The median age of non-survivor group (NSG) was higher than survivor group (SG) [66.0 years (Q1 -Q3: 55.0-77.5) vs 54.0 years (Q1 -Q3: 43.0-63.0)] (p < 0.001). Study parameters which were measured significantly higher in the NSG were CRP, cTnI, triglyceride, CRI-I, CRI-II, AC, AIP, ferritin, CAR, MHR and THR. LDLc, HDLc, TC and albumin were significantly lower in NSG (p<0.001). CONCLUSION: THR is positively correlated with myocardial damage and strongly predicts in-hospital mortality in COVID-19.


Assuntos
Aterosclerose , Proteína C-Reativa , COVID-19 , Mortalidade Hospitalar , Humanos , COVID-19/mortalidade , COVID-19/patologia , COVID-19/sangue , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Idoso , Aterosclerose/mortalidade , Aterosclerose/sangue , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Triglicerídeos/sangue , Troponina I/sangue , SARS-CoV-2/isolamento & purificação , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Miocárdio/patologia , Miocárdio/metabolismo , Adulto
9.
PLoS One ; 19(5): e0302475, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38748685

RESUMO

Cardiac troponin I (cTnI) is a cardiac biomarker for diagnosing ischemic heart disease and acute myocardial infarction. Current biochemical assays use antibodies (Abs) due to their high specificity and sensitivity. However, there are some limitations, such as the high-cost production of Abs due to complex instruments, reagents, and steps; the variability of Abs quality from batch to batch; the low stability at high temperatures; and the difficulty of chemical modification. Aptamer overcomes the limitations of antibodies, such as relatively lower cost, high reproducibility, high stability, and ease of being chemically modified. Aptamers are three-dimensional architectures of single-stranded RNA or DNA that bind to targets such as proteins. Six aptamers (Tro1-Tro6) with higher binding affinity than an antibody have been identified, but the molecular interaction has not been studied. In this study, six DNA aptamers were modeled and docked to cTnI protein. Molecular docking revealed that the interaction between all aptamer and cTnI happened in the similar cTnI region. The interaction between aptamer and cTnI involved hydrophobic interaction, hydrogen bonds, π-cation interactions, π-stack interactions, and salt-bridge formation. The calculated binding energy of all complexes was negative, which means that the complex formation was thermodynamically favorable. The electrostatic energy term was the main driving force of the interaction between all aptamer and cTnI. This study could be used to predict the behavior of further modified aptamer to improve aptamer performance.


Assuntos
Aptâmeros de Nucleotídeos , DNA de Cadeia Simples , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Troponina I , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/metabolismo , Troponina I/metabolismo , Troponina I/química , DNA de Cadeia Simples/química , DNA de Cadeia Simples/metabolismo , Humanos , Ligação de Hidrogênio , Ligação Proteica , Termodinâmica
10.
J Am Heart Assoc ; 13(9): e032172, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38700022

RESUMO

BACKGROUND: The purpose of this study was to investigate a therapeutic approach targeting the inflammatory response and consequent remodeling from ischemic myocardial injury. METHODS AND RESULTS: Coronary thrombus aspirates were collected from patients at the time of ST-segment-elevation myocardial infarction and subjected to array-based proteome analysis. Clinically indistinguishable at myocardial infarction (MI), patients were stratified into vulnerable and resilient on the basis of 1-year left ventricular ejection fraction and death. Network analysis from coronary aspirates revealed prioritization of tumor necrosis factor-α signaling in patients with worse clinical outcomes. Infliximab, a tumor necrosis factor-α inhibitor, was infused intravenously at reperfusion in a porcine MI model to assess whether infliximab-mediated immune modulation impacts post-MI injury. At 3 days after MI (n=7), infliximab infusion increased proregenerative M2 macrophages in the myocardial border zone as quantified by immunofluorescence (24.1%±23.3% in infliximab versus 9.29%±8.7% in sham; P<0.01). Concomitantly, immunoassays of coronary sinus samples quantified lower troponin I levels (41.72±7.34 pg/mL versus 58.11±10.75 pg/mL; P<0.05) and secreted protein analysis revealed upregulation of injury-modifying interleukin-2, -4, -10, -12, and -18 cytokines in the infliximab-treated cohort. At 4 weeks (n=12), infliximab treatment resulted in significant protective influence, improving left ventricular ejection fraction (53.9%±5.4% versus 36.2%±5.3%; P<0.001) and reducing scar size (8.31%±10.9% versus 17.41%±12.5%; P<0.05). CONCLUSIONS: Profiling of coronary thrombus aspirates in patients with ST-segment-elevation MI revealed highest association for tumor necrosis factor-α in injury risk. Infliximab-mediated immune modulation offers an actionable pathway to alter MI-induced inflammatory response, preserving contractility and limiting adverse structural remodeling.


Assuntos
Modelos Animais de Doenças , Infliximab , Remodelação Ventricular , Infliximab/uso terapêutico , Infliximab/farmacologia , Animais , Humanos , Masculino , Pessoa de Meia-Idade , Remodelação Ventricular/efeitos dos fármacos , Feminino , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/imunologia , Função Ventricular Esquerda/efeitos dos fármacos , Suínos , Idoso , Fator de Necrose Tumoral alfa/metabolismo , Volume Sistólico/efeitos dos fármacos , Trombose Coronária/prevenção & controle , Trombose Coronária/tratamento farmacológico , Miocárdio/patologia , Miocárdio/metabolismo , Miocárdio/imunologia , Troponina I/sangue , Troponina I/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo
11.
Sci Transl Med ; 16(741): eadg2841, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38569017

RESUMO

Troponin I (TnI) regulates thin filament activation and muscle contraction. Two isoforms, TnI-fast (TNNI2) and TnI-slow (TNNI1), are predominantly expressed in fast- and slow-twitch myofibers, respectively. TNNI2 variants are a rare cause of arthrogryposis, whereas TNNI1 variants have not been conclusively established to cause skeletal myopathy. We identified recessive loss-of-function TNNI1 variants as well as dominant gain-of-function TNNI1 variants as a cause of muscle disease, each with distinct physiological consequences and disease mechanisms. We identified three families with biallelic TNNI1 variants (F1: p.R14H/c.190-9G>A, F2 and F3: homozygous p.R14C), resulting in loss of function, manifesting with early-onset progressive muscle weakness and rod formation on histology. We also identified two families with a dominantly acting heterozygous TNNI1 variant (F4: p.R174Q and F5: p.K176del), resulting in gain of function, manifesting with muscle cramping, myalgias, and rod formation in F5. In zebrafish, TnI proteins with either of the missense variants (p.R14H; p.R174Q) incorporated into thin filaments. Molecular dynamics simulations suggested that the loss-of-function p.R14H variant decouples TnI from TnC, which was supported by functional studies showing a reduced force response of sarcomeres to submaximal [Ca2+] in patient myofibers. This contractile deficit could be reversed by a slow skeletal muscle troponin activator. In contrast, patient myofibers with the gain-of-function p.R174Q variant showed an increased force to submaximal [Ca2+], which was reversed by the small-molecule drug mavacamten. Our findings demonstrated that TNNI1 variants can cause muscle disease with variant-specific pathomechanisms, manifesting as either a hypo- or a hypercontractile phenotype, suggesting rational therapeutic strategies for each mechanism.


Assuntos
Doenças Musculares , Sarcômeros , Animais , Humanos , Cálcio/metabolismo , Contração Muscular , Músculo Esquelético/metabolismo , Doenças Musculares/genética , Sarcômeros/metabolismo , Troponina I/genética , Troponina I/metabolismo , Peixe-Zebra/metabolismo
12.
Physiol Rep ; 12(7): e15990, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38575554

RESUMO

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are rapidly gaining ground in the treatment of heart failure (HF) with reduced ejection fraction (HFrEF) and acute myocardial infarction (AMI) by an unknown mechanism. Upregulation of Na+/H+ exchanger 1 (NHE1), SGLT1, and Ca2+/calmodulin-dependent protein kinase II (CaMKII) in the diseased hearts was found to be attenuated by prolonged SGLT2i treatment. Unfortunately, dapagliflozin is not well understood as to how Na+/Ca2+ homeostasis is affected in cardiomyocytes. In this study, we aimed to investigate whether mechanical stretch in cardiomyocytes upregulate SGLT2, resulted to loss of Na+/Ca2+ homeostasis via ERK and eNOS signaling. AMI (+) and AMI (-) serum levels were estimated using ELISA assays of TGFß-1 or endoglin (CD105). Human cardiomyocyte cell line AC16 was subjected to different stresses: 5% mild and 25% aggressive, at 1 Hz for 24 h. Immunofluorescence assays were used to estimate troponin I, CD105, SGLT1/2, eNOSS633, and ERK1/2T202/Y204 levels was performed for 5% (mild), and 25% elongation for 24 h. AMI (+) serum showed increased TGFß1 and CD105 compared to AMI (-) patients. In consistent, troponin I, CD105, SGLT1/2, eNOSS633 and ERK1/2T202/Y204 were upregulated after 25% of 24 h cyclic stretch. Dapagliflozin addition caused SGLT2 inhibition, which significantly decreased troponin I, CD105, SGLT1/2, eNOSS633, and ERK1/2T202/Y204 under 25% cyclic stretching. In summary, SGLT2 may have sensed mechanical stretch in a way similar to cardiac overloading as in vivo. By blocking SGLT2 in stretched cardiomyocytes, the AMI biomarkers (CD105, troponin I and P-ERK) were decreased, potentially to rescue eNOS production to maintain normal cellular function. This discovery of CD105 and SGLT2 increase in mechanically stretched cardiomyocytes suggests that SGLT2 may conceive a novel role in direct or indirect sensing of mechanical stretch, prompting the possibility of an in vitro cardiac overloaded cell model, an alternative to animal heart model.


Assuntos
Compostos Benzidrílicos , Glucosídeos , Insuficiência Cardíaca , Infarto do Miocárdio , Humanos , Animais , Endoglina/metabolismo , Insuficiência Cardíaca/metabolismo , Regulação para Cima , Transportador 2 de Glucose-Sódio/metabolismo , Troponina I/metabolismo , Volume Sistólico , Miócitos Cardíacos/metabolismo
13.
Ann Intern Med ; 177(4): JC41, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38560903

RESUMO

SOURCE CITATION: Lee KK, Doudesis D, Ferry AV, et al; High-STEACS Investigators. Implementation of a high sensitivity cardiac troponin I assay and risk of myocardial infarction or death at five years: observational analysis of a stepped wedge, cluster randomised controlled trial. BMJ. 2023;383:e075009. 38011922.


Assuntos
Síndrome Coronariana Aguda , Infarto do Miocárdio , Humanos , Troponina I , Biomarcadores , Infarto do Miocárdio/diagnóstico , Troponina T
14.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(2): 307-312, 2024 Apr 18.
Artigo em Chinês | MEDLINE | ID: mdl-38595249

RESUMO

OBJECTIVE: To investigate the risk factors of acute respiratory distress syndrome (ARDS) after traumatic hemorrhagic shock. METHODS: This was a retrospective cohort study of 314 patients with traumatic hemorrhagic shock at Trauma Medicine Center, Peking University People's Hospital from December 2012 to August 2021, including 152 male patients and 162 female patients, with a median age of 63.00 (49.75-82.00) years. The demographic data, past medical history, injury assessment, vital signs, laboratory examination and other indicators of these patients during hospitalization were recorded. These patients were divided into two groups, ARDS group (n=89) and non-ARDS group (n=225) according to whether there was ARDS within 7 d of admission. Risk factors for ARDS were identified using Logistic regression. The C-statistic expressed as a percentage [area under curve (AUC) of the receiver operating characteristic (ROC) curve] was used to assess the discrimination of the model. RESULTS: The incidence of ARDS after traumatic hemorrhagic shock was 28.34%. Finally, Logistic regression model showed that the independent risk factors of ARDS after traumatic hemorrhagic shock included male, history of coronary heart disease, high acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, road traffic accident and elevated troponin Ⅰ. The OR and 95% confidence intervals (CI) were 4.01 (95%CI: 1.75-9.20), 5.22 (95%CI: 1.29-21.08), 1.07 (95%CI: 1.02-1.57), 2.53 (95%CI: 1.21-5.28), and 1.26 (95%CI: 1.02-1.57), respectively; the P values were 0.001, 0.020, 0.009, 0.014, and 0.034, respectively. The ROC curve was used to analyze the value of each risk factor in predicting ARDS. It was found that the AUC for predicting ARDS after traumatic hemorrhagic shock was 0.59 (95%CI: 0.51-0.68) for male, 0.55 (95%CI: 0.46-0.64) for history of coronary heart disease, 0.65 (95%CI: 0.57-0.73) for APACHE Ⅱ score, 0.58 (95%CI: 0.50-0.67) for road traffic accident, and 0.73 (95%CI: 0.66-0.80) for elevated troponin Ⅰ, with an overall predictive value of 0.81 (95%CI: 0.74-0.88). CONCLUSION: The incidence of ARDS in patients with traumatic hemorrhagic shock is high, and male, history of coronary heart disease, high APACHE Ⅱ score, road traffic accident and elevated troponin Ⅰ are independent risk factors for ARDS after traumatic hemorrhagic shock. Timely monitoring these indicators is conducive to early detection and treatment of ARDS after traumatic hemorrhagic shock.


Assuntos
Doença das Coronárias , Síndrome do Desconforto Respiratório , Choque Hemorrágico , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Choque Hemorrágico/complicações , Estudos Retrospectivos , Troponina I , Síndrome do Desconforto Respiratório/etiologia , Curva ROC , Prognóstico , Fatores de Risco
15.
Biosens Bioelectron ; 256: 116262, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38621340

RESUMO

Lateral flow immunoassays (LFIAs) are an essential and widely used point-of-care test for medical diagnoses. However, commercial LFIAs still have low sensitivity and specificity. Therefore, we developed an automatic ultrasensitive dual-color enhanced LFIA (DCE-LFIA) by applying an enzyme-induced tyramide signal amplification method to a double-antibody sandwich LFIA for antigen detection. The DCE-LFIA first specifically captured horseradish peroxidase (HRP)-labeled colored microspheres at the Test line, and then deposited a large amount of tyramide-modified signals under the catalytic action of HRP to achieve the color superposition. A limit of detection (LOD) of 3.9 pg/mL and a naked-eye cut-off limit of 7.8 pg/mL were achieved for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein. Additionally, in the inactivated virus detections, LOD equivalent to chemiluminescence (0.018 TCID50/mL) was obtained, and it had excellent specificity under the interference of other respiratory viruses. High sensitivity has also been achieved for detection of influenza A, influenza B, cardiac troponin I, and human chorionic gonadotrophin using this DCE-LFIA, suggesting the assay is universally applicable. To ensure the convenience and stability in practical applications, we created an automatic device. It provides a new practical option for point-of-care test immunoassays, especially ultra trace detection and at-home testing.


Assuntos
Técnicas Biossensoriais , COVID-19 , Limite de Detecção , SARS-CoV-2 , Imunoensaio/instrumentação , Imunoensaio/métodos , Humanos , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/imunologia , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , COVID-19/diagnóstico , COVID-19/virologia , Peroxidase do Rábano Silvestre/química , Troponina I/sangue , Troponina I/análise , Testes Imediatos , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/análise , Gonadotropina Coriônica/análise , Gonadotropina Coriônica/sangue , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza A/imunologia , Fosfoproteínas
16.
BMJ Open ; 14(4): e082220, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38658000

RESUMO

OBJECTIVE: There is a need for a robust tool to stratify the patient's risk with COVID-19. We assessed the prognostic values of cardiac biomarkers for COVID-19 patients. METHODS: This is a single-centre retrospective cohort study. Consecutive laboratory-confirmed COVID-19 patients admitted to the Kobe City Medical Center General Hospital from July 2020 to September 2021 were included. We obtained cardiac biomarker values from electronic health records and institutional blood banks. We stratified patients with cardiac biomarkers as high-sensitive troponin I (hsTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatine kinase (CK) and CK myocardial band (CK-MB), using the clinically relevant thresholds. Prespecified primary outcome measure was all-cause death. RESULTS: A total of 917 patients were included. hsTnI, NT-proBNP, CK and CK-MB were associated with the significantly higher cumulative 30-day incidence of all-cause death (hsTnI: <5.0 ng/L group; 4.3%, 5.0 ng/L-99%ile upper reference limit (URL) group; 8.8% and ≥99% ile URL group; 25.2%, p<0.001. NT-proBNP: <125 pg/mL group; 5.3%, 125-900 pg/mL group; 10.5% and ≥900 pg/mL group; 31.9%, p<0.001. CK:

Assuntos
Biomarcadores , COVID-19 , Creatina Quinase Forma MB , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , SARS-CoV-2 , Troponina I , Humanos , COVID-19/mortalidade , COVID-19/sangue , COVID-19/diagnóstico , Feminino , Masculino , Biomarcadores/sangue , Estudos Retrospectivos , Prognóstico , Idoso , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Troponina I/sangue , Pessoa de Meia-Idade , Medição de Risco/métodos , Creatina Quinase Forma MB/sangue , Creatina Quinase/sangue , Idoso de 80 Anos ou mais
17.
Transpl Int ; 37: 12724, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38665474

RESUMO

Trends in high-sensitivity cardiac troponin I (hs-cTnI) after lung transplant (LT) and its clinical value are not well stablished. This study aimed to determine kinetics of hs-cTnI after LT, factors impacting hs-cTnI and clinical outcomes. LT recipients from 2015 to 2017 at Toronto General Hospital were included. Hs-cTnI levels were collected at 0-24 h, 24-48 h and 48-72 h after LT. The primary outcome was invasive mechanical ventilation (IMV) >3 days. 206 patients received a LT (median age 58, 35.4% women; 79.6% double LT). All patients but one fulfilled the criteria for postoperative myocardial infarction (median peak hs-cTnI = 4,820 ng/mL). Peak hs-cTnI correlated with right ventricular dysfunction, >1 red blood cell transfusions, bilateral LT, use of EVLP, kidney function at admission and time on CPB or VA-ECMO. IMV>3 days occurred in 91 (44.2%) patients, and peak hs-cTnI was higher in these patients (3,823 vs. 6,429 ng/mL, p < 0.001 after adjustment). Peak hs-cTnI was higher among patients with had atrial arrhythmias or died during admission. No patients underwent revascularization. In summary, peak hs-TnI is determined by recipient comorbidities and perioperative factors, and not by coronary artery disease. Hs-cTnI captures patients at higher risk for prolonged IMV, atrial arrhythmias and in-hospital death.


Assuntos
Transplante de Pulmão , Troponina I , Humanos , Transplante de Pulmão/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Troponina I/sangue , Idoso , Adulto , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Infarto do Miocárdio/sangue , Biomarcadores/sangue , Respiração Artificial
18.
J Cell Mol Med ; 28(9): e18357, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38683127

RESUMO

In our previous study, intranuclear cardiac troponin I (cTnI) may function as a co-factor of Yin Yang 1(YY1). Here, we aimed to explore the role of intranuclear cTnI in ageing hearts. Nuclear translocation of cTnI was demonstrated using Western blot and immunofluorescence. The potential nuclear localization sequences (NLSs) of cTnI were predicted by a web server and then verified in 293T cells by putative NLS-eGFP-GST and NLS-mutant transfection. The ratio of Nuclear cTnI/ Total cTnI (Nu/T) decreased significantly in ageing hearts, accompanied with ATG5-decline-related impaired cardiac autophagy. RNA sequencing was performed in cTnI knockout hearts. The differential expressed genes (DEGs) were analysed by overlapping with YY1 ChIP-sequencing data. cTnI gain and loss experiments in vitro determined those filtered DEGs' expression levels. A strong correlation was found between expression patterns cTnI and FOS. Using ChIP-q-PCR, we demonstrated that specific binding DNA sequences of cTnI were enriched in the FOS promoter -299 to -157 region. It was further verified that pcDNA3.1 (-)-cTnI could increase the promoter activity of FOS by using luciferase report assay. At last, we found that FOS can regulate the ATG5 (autophagy-related gene 5) gene by using a luciferase report assay. Taken together, our results indicate that decreased intranuclear cTnI in ageing hearts may cause impaired cardiac autophagy through the FOS/ATG5 pathway.


Assuntos
Envelhecimento , Proteína 5 Relacionada à Autofagia , Autofagia , Núcleo Celular , Miocárdio , Troponina I , Troponina I/metabolismo , Troponina I/genética , Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína 5 Relacionada à Autofagia/genética , Envelhecimento/metabolismo , Envelhecimento/genética , Animais , Miocárdio/metabolismo , Humanos , Núcleo Celular/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Camundongos , Células HEK293 , Masculino , Regiões Promotoras Genéticas , Regulação da Expressão Gênica , Miócitos Cardíacos/metabolismo , Camundongos Knockout
19.
Talanta ; 274: 126040, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38581853

RESUMO

Rapid and sensitive detection of multiple biomarkers by lateral flow immunoassay (LFIA) remains challenging for signal amplification for commonly used nanotags. Herein, we report a novel LFIA strip for visual and highly sensitive analysis of two cardiac biomarkers based on functionalized gold nanoparticles @ polystyrene microsphere (Au@PS)microcavity as surface-enhanced Raman scattering (SERS) tags. Antibody-modified Au@PS was designed as a SERS label. The evanescent waves propagating along the surface of the PS microcavity and the localized surface plasmons of the gold nanoparticles were coupled to enhance the light-matter interaction synergistically for Raman signal enhancement. In this strategy, the proposed Au@PS SERS tags-based LFIA was carried out to quantify the content of the heart failure and infarct biomarkers synchronously within 15 min and get the limits of detection of 1 pg/mL and 10 pg/mL for cardiac troponin I (cTnI) and N-terminal natriuretic peptide precursor (NT-proBNP), respectively. The results demonstrated 10-20 folds more sensitivity than that of the standard colloidal gold strip and fluorescent strip for the same biomarkers. This novel quantitative LFIA shows promise as a high-sensitive and visual sensing method for relevant clinical and forensic analysis.


Assuntos
Biomarcadores , Ouro , Nanopartículas Metálicas , Peptídeo Natriurético Encefálico , Poliestirenos , Análise Espectral Raman , Troponina I , Ouro/química , Imunoensaio/métodos , Troponina I/análise , Troponina I/sangue , Biomarcadores/análise , Poliestirenos/química , Análise Espectral Raman/métodos , Humanos , Peptídeo Natriurético Encefálico/análise , Peptídeo Natriurético Encefálico/sangue , Nanopartículas Metálicas/química , Fragmentos de Peptídeos/análise , Microesferas , Limite de Detecção , Insuficiência Cardíaca
20.
Clin Chim Acta ; 558: 117900, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38580139

RESUMO

BACKGROUND: Measurement of cardiac troponin (cTn) by a high sensitivity method is now the recommended strategy for the detection of myocardial injury. An international survey was undertaken to assess how this has been implemented. METHODS: A questionnaire based around 14 domains on cardiac biomarkers was distributed electronically with the aid of professional societies accessed by a web link within the invitation. Results were returned electronically then extracted into a relational database for analysis. RESULTS: Responses were obtained from 663 laboratories across 76 countries ranging from 1 to 69 largest country. The majority of responses (79.6%) came from the European area. Responses were grouped into broad geographic areas for analysis. Most responses came from hospitals providing a local and regional service of which the majority provided angioplasty. cTn measurement was the dominant biomarker. The majority of laboratories include creatine kinase (CK) in their cardiac profile and approximately 50% also offer the MB isoenzyme of CK. The majority of laboratories (91.9%) measure cTn by a high sensitivity method. Sex specific reference ranges were typically implemented for cardiac troponin I but not for cardiac troponin T. The preferred unit of measurement was nanograms/L. A structured decision-making pathway utilising high sensitivity cTn measurement was used by 83.3% of laboratories who responded. Single sample rule out is common but the majority used serial sampling strategy based on measurement on admission and three hours. CONCLUSIONS: Measurement of cTn by a high sensitivity method is now well established internationally, the use of rapid diagnostic protocols lags behind.


Assuntos
Biomarcadores , Humanos , Biomarcadores/sangue , Europa (Continente) , Inquéritos e Questionários , Troponina/sangue , Troponina/análise , Guias de Prática Clínica como Assunto , Troponina T/sangue , Troponina I/sangue
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...