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1.
Oxid Med Cell Longev ; 2021: 6957900, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603600

RESUMO

Macrophage polarization in response to environmental cues has emerged as an important event in the development of atherosclerosis. Compelling evidences suggest that P21-activated kinases 1 (PAK1) is involved in a wide variety of diseases. However, the potential role and mechanism of PAK1 in regulation of macrophage polarization remains to be elucidated. Here, we observed that PAK1 showed a dramatically increased expression in M1 macrophages but decreased expression in M2 macrophages by using a well-established in vitro model to study heterogeneity of macrophage polarization. Adenovirus-mediated loss-of-function approach demonstrated that PAK1 silencing induced an M2 macrophage phenotype-associated gene profiles but repressed the phenotypic markers related to M1 macrophage polarization. Additionally, dramatically decreased foam cell formation was found in PAK1 silencing-induced M2 macrophage activation which was accompanied with alternation of marker account for cholesterol efflux or influx from macrophage foam cells. Moderate results in lipid metabolism and foam cell formation were found in M1 macrophage activation mediated by AdshPAK1. Importantly, we presented mechanistic evidence that PAK1 knockdown promoted the expression of PPARγ, and the effect of macrophage activation regulated by PAK1 silencing was largely reversed when a PPARγ antagonist was utilized. Collectively, these findings reveal that PAK1 is an independent effector of macrophage polarization at least partially attributed to regulation of PPARγ expression, which suggested PAK1-PPARγ axis as a novel therapeutic strategy in atherosclerosis management.

2.
Cell Metab ; 33(10): 2059-2075.e10, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34536344

RESUMO

Myocardial ischemia-reperfusion (MIR) injury is a major cause of adverse outcomes of revascularization after myocardial infarction. To identify the fundamental regulator of reperfusion injury, we performed metabolomics profiling in plasma of individuals before and after revascularization and identified a marked accumulation of arachidonate 12-lipoxygenase (ALOX12)-dependent 12-HETE following revascularization. The potent induction of 12-HETE proceeded by reperfusion was conserved in post-MIR in mice, pigs, and monkeys. While genetic inhibition of Alox12 protected mouse hearts from reperfusion injury and remodeling, Alox12 overexpression exacerbated MIR injury. Remarkably, pharmacological inhibition of ALOX12 significantly reduced cardiac injury in mice, pigs, and monkeys. Unexpectedly, ALOX12 promotes cardiomyocyte injury beyond its enzymatic activity and production of 12-HETE but also by its suppression of AMPK activity via a direct interaction with its upstream kinase TAK1. Taken together, our study demonstrates that ALOX12 is a novel AMPK upstream regulator in the post-MIR heart and that it represents a conserved therapeutic target for the treatment of myocardial reperfusion injury.

3.
J Cardiovasc Electrophysiol ; 32(7): 1849-1856, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34028114

RESUMO

INTRODUCTION: Linear ablation in addition to pulmonary vein antrum isolation (PVAI) has failed to improve the success rate for persistent atrial fibrillation (PeAF), due to incomplete block of ablation lines, especially in the mitral isthmus (MI). METHODS AND RESULTS: The study enrolled 191 patients (66 in group 1 and 125 in group 2). In group 1, ethanol infusion into the vein of Marshall was first performed, followed by radiofrequency (RF) applications targeting bilateral PVAI and bidirectional block in the roofline, cavotricuspid isthmus, and MI. In group 2, PVAI and the three linear ablations were completed using only RF energy. MI block was achieved in 63 (95.5%) and 101 (80.8%) patients in groups 1 and 2, respectively (p = .006). Patients in group 1 had shorter ablation time for left pulmonary vein antrum (8.15 vs. 12.59 min, p < .001) and MI (7.0 vs. 11.8 min, p < .001) and required less cardioversion (50 [78.5%] vs. 113 [90.4%], p = .007). During the 12-month follow-up, 58 (87.9%) patients were free from atrial fibrillation/atrial tachycardia in group 1 compared with 81 (64.8%) in group 2 (p < .001). In multivariate cox regression, the "upgraded 2C3L" procedure is associated with a lower recurrence rate (hazard ratio = 0.27, 95% confidence interval = 0.12-0.59). CONCLUSION: Compared with the conventional "2C3L" approach, the "upgraded 2C3L" approach has higher effectiveness for ablation of PeAF.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Etanol/efeitos adversos , Humanos , Veias Pulmonares/cirurgia , Recidiva , Taquicardia , Resultado do Tratamento
4.
Circ Res ; 128(11): 1747-1765, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34043417

RESUMO

Cardiac arrhythmias and the resulting sudden cardiac death are significant cardiovascular complications that continue to impose a heavy burden on patients and society. An emerging body of evidence indicates that nonalcoholic fatty liver disease (NAFLD) is closely associated with the risk of cardiac arrhythmias, independent of other conventional cardiometabolic comorbidities. Although most studies focus on the relationship between NAFLD and atrial fibrillation, associations with ventricular arrhythmias and cardiac conduction defects have also been reported. Mechanistic investigations suggest that a number of NAFLD-related pathophysiological alterations may potentially elicit structural, electrical, and autonomic remodeling in the heart, contributing to arrhythmogenic substrates in the heart. NAFLD is now the most common liver and metabolic disease in the world. However, the upsurge in the prevalence of NAFLD as an emerging risk factor for cardiac arrhythmias has received little attention. In this review, we summarize the clinical evidence and putative pathophysiological mechanisms for the emerging roles of NAFLD in cardiac arrhythmias, with the purpose of highlighting the notion that NAFLD may serve as an independent risk factor and a potential driving force in the development and progression of cardiac arrhythmias.

5.
Am J Hypertens ; 34(3): 282-290, 2021 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-33386395

RESUMO

BACKGROUND: The risk that coronavirus disease 2019 (COVID-19) patients develop critical illness that can be fatal depends on their age and immune status and may also be affected by comorbidities like hypertension. The goal of this study was to develop models that predict outcome using parameters collected at admission to the hospital. METHODS AND RESULTS: This is a retrospective single-center cohort study of COVID-19 patients at the Seventh Hospital of Wuhan City, China. Forty-three demographic, clinical, and laboratory parameters collected at admission plus discharge/death status, days from COVID-19 symptoms onset, and days of hospitalization were analyzed. From 157 patients, 120 were discharged and 37 died. Pearson correlations showed that hypertension and systolic blood pressure (SBP) were associated with death and respiratory distress parameters. A penalized logistic regression model efficiently predicts the probability of death with 13 of 43 variables. A regularized Cox regression model predicts the probability of survival with 7 of above 13 variables. SBP but not hypertension was a covariate in both mortality and survival prediction models. SBP was elevated in deceased compared with discharged COVID-19 patients. CONCLUSIONS: Using an unbiased approach, we developed models predicting outcome of COVID-19 patients based on data available at hospital admission. This can contribute to evidence-based risk prediction and appropriate decision-making at hospital triage to provide the most appropriate care and ensure the best patient outcome. High SBP, a cause of end-organ damage and an important comorbid factor, was identified as a covariate in both mortality and survival prediction models.


Assuntos
Pressão Sanguínea , COVID-19/diagnóstico , Estado Terminal/mortalidade , Testes Diagnósticos de Rotina , Hipertensão , Medição de Risco/métodos , Determinação da Pressão Arterial/métodos , Determinação da Pressão Arterial/estatística & dados numéricos , COVID-19/epidemiologia , COVID-19/fisiopatologia , COVID-19/terapia , China/epidemiologia , Comorbidade , Testes Diagnósticos de Rotina/métodos , Testes Diagnósticos de Rotina/estatística & dados numéricos , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , SARS-CoV-2/isolamento & purificação , Análise de Sobrevida
6.
Heart Fail Rev ; 26(2): 371-380, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32844337

RESUMO

The coronavirus disease (COVID-19) pandemic is a global health priority. Given that cardiovascular diseases (CVD) are the leading cause of morbidity around the world and that several trials have reported severe cardiovascular damage in patients infected with SARS-CoV-2, a substantial number of COVID-19 patients with underlying cardiovascular diseases need to continue their medications in order to improve myocardial contractility and to prevent the onset of major adverse cardiovascular events (MACEs), including heart failure. Some of the current life-saving medications may actually simultaneously expose patients to a higher risk of severe COVID-19. Angiotensin-converting enzyme 2 (ACE2), a key counter regulator of the renin-angiotensin system (RAS), is the main entry gate of SARS-CoV-2 into human host cells and an established drug target to prevent heart failure. In fact, ACE inhibitors, angiotensin II receptor blockers, and mineralocorticoid antagonists may augment ACE2 levels to protect organs from angiotensin II overload. Elevated ACE2 expression on the host cell surface might facilitate viral entrance, at the same time sudden nonadherence to these medications triggers MACEs. Hence, safety issues in the use of RAS inhibitors in COVID-19 patients with cardiac dysfunction remain an unsolved dilemma and need paramount attention. Although ACE2 generally plays an adaptive role in both healthy subjects and patients with systolic and/or diastolic dysfunction, we conducted a literature appraisal on its maladaptive role. Understanding the exact role of ACE2 in COVID-19 patients at risk of heart failure is needed to safely manage RAS inhibitors in frail and non-frail critically ill patients.


Assuntos
Enzima de Conversão de Angiotensina 2/antagonistas & inibidores , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , COVID-19/induzido quimicamente , COVID-19/epidemiologia , Insuficiência Cardíaca/tratamento farmacológico , Enzima de Conversão de Angiotensina 2/fisiologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Humanos , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia , Medição de Risco
7.
Pacing Clin Electrophysiol ; 44(5): 792-799, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32914878

RESUMO

The ligament of Marshall (LOM) is a remnant of the embryonic sinus venosus and left cardinal vein, and contains fat and fibrous tissues, blood vessels, muscle bundles, nerve fibers, and ganglia. The complexity of LOM's structure makes it as a source of triggers and drivers as well as substrates of re-entry for atrial arrhythmias, especially for atrial fibrillation (AF). LOM also serves as a portion of left atrial macro-re-entrant circuit, especially peri-mitral isthmus re-entrant circuit. Experimental studies demonstrate that the LOM acts as a sympathetic conduit between the left stellate ganglion and the ventricles, and participates in the initiation and maintenance of ventricular arrhythmias. Endocardial or epicardial catheter ablation or ethanol infusion into the vein of Marshall may serve as an important adjunct therapy to pulmonary vein isolation in patients with advanced stage of AF, and may help alleviate ventricular arrhythmias as well.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33191522

RESUMO

BACKGROUND: In randomized studies, the strategy of pulmonary vein (PV) antral isolation (PVI) plus linear ablation has failed to increase success rates for persistent atrial fibrillation (PeAF) ablation when compared with PVI alone. Peri-mitral reentry related atrial tachycardia due to incomplete linear block is an important cause of clinical failures of a first ablation procedure. Ethanol infusion (EI) into the vein of Marshall (EI-VOM) has been demonstrated to facilitate a durable mitral isthmus linear lesion. OBJECTIVE: This trial is designed to compare arrhythmia-free survival between PVI and an ablation strategy termed upgraded '2C3L' for ablation of PeAF. STUDY DESIGN: The PROMPT-AF study is a prospective, multicenter, randomized trial involving blinded assessment of outcomes. Patients (n = 276) undergoing their first catheter ablation of PeAF will be randomized to either the upgraded '2C3L' arm or PVI arm in a 1:1 fashion. The upgraded '2C3L' technique is a fixed ablation approach consisting of EI-VOM, bilateral circumferential PVI and three linear ablation lesion sets across the mitral isthmus, left atrial roof, and cavo-tricuspid isthmus. The follow-up duration is 12 months. The primary endpoint is the rate of documented atrial tachycardia arrhythmias of >30 seconds, without any antiarrhythmic drugs, in 12 months after the index ablation procedure (excluding a blanking period of 3 months). CONCLUSIONS: The PROMPT-AF study will evaluate the efficacy of the fixed '2C3L' approach in conjunction with EI-VOM, compared with PVI alone, in patients with PeAF undergoing de novo ablation. This article is protected by copyright. All rights reserved.

9.
J Arrhythm ; 36(5): 827-836, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33024460

RESUMO

The emergence of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a major global public health concern. Although SARS-CoV-2 causes primarily respiratory problems, concurrent cardiac injury cannot be ignored since it may be an independent predictor for adverse outcomes. Cardiac arrhythmias are often observed in patients with COVID-19, especially in severe cases, and more likely contribute to the high risk of adverse outcomes. Arrhythmias should be regarded as one of the main complications of COVID-19. Mechanistically, a number of ion channels can be adversely affected in COVID-19, leading to alterations in cardiac conduction and/or repolarization properties, as well as calcium handling, which can predispose to cardiac arrhythmogenesis. In addition, several antimicrobials that are currently used as potential therapeutic agents for COVID-19, such as chloroquine, hydroxychloroquine and azithromycin, have uncertain benefit, and yet may induce electrocardiographic QT prolongation with potential ventricular pro-arrhythmic effects. Continuous electrocardiogram monitoring, accurate and prompt recognition of arrhythmias are important. The present review focuses on cardiac arrhythmias in patients with COVID-19, its underlying mechanisms, and proposed preventive and therapeutic strategies.

12.
J Am Heart Assoc ; 9(16): e016419, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32805187

RESUMO

Background The development of pathological cardiac hypertrophy involves the coordination of a series of transcription activators and repressors, while their interplay to trigger pathological gene reprogramming remains unclear. NULP1 (nuclear localized protein 1) is a member of the basic helix-loop-helix family of transcription factors and its biological functions in pathological cardiac hypertrophy are barely understood. Methods and Results Immunoblot and immunostaining analyses showed that NULP1 expression was consistently reduced in the failing hearts of patients and hypertrophic mouse hearts and rat cardiomyocytes. Nulp1 knockout exacerbates aortic banding-induced cardiac hypertrophy pathology, which was significantly blunted by transgenic overexpression of Nulp1. Signal pathway screening revealed the nuclear factor of activated T cells (NFAT) pathway to be dramatically suppressed by NULP1. Coimmunoprecipitation showed that NULP1 directly interacted with the topologically associating domain of NFAT3 via its C-terminal region, which was sufficient to suppress NFAT3 transcriptional activity. Inactivation of the NFAT pathway by VIVIT peptides in vivo rescued the aggravated pathogenesis of cardiac hypertrophy resulting from Nulp1 deficiency. Conclusions NULP1 is an endogenous suppressor of NFAT3 signaling under hypertrophic stress and thus negatively regulates the pathogenesis of cardiac hypertrophy. Targeting overactivated NFAT by NULP1 may be a novel therapeutic strategy for the treatment of pathological cardiac hypertrophy and heart failure.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Cardiomegalia/metabolismo , Fatores de Transcrição NFATC/metabolismo , Proteínas Repressoras/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/deficiência , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Cardiomegalia/diagnóstico por imagem , Cardiomegalia/genética , Cardiomegalia/terapia , Ecocardiografia , Deleção de Genes , Humanos , Imunoprecipitação/métodos , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Miócitos Cardíacos/metabolismo , Fatores de Transcrição NFATC/antagonistas & inibidores , Fatores de Transcrição NFATC/genética , Oligopeptídeos/farmacologia , Monoéster Fosfórico Hidrolases/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas Repressoras/deficiência , Proteínas Repressoras/genética , Transcrição Genética
13.
Cell Metab ; 32(4): 537-547.e3, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32861268

RESUMO

The safety and efficacy of anti-diabetic drugs are critical for maximizing the beneficial impacts of well-controlled blood glucose on the prognosis of individuals with COVID-19 and pre-existing type 2 diabetes (T2D). Metformin is the most commonly prescribed first-line medication for T2D, but its impact on the outcomes of individuals with COVID-19 and T2D remains to be clarified. Our current retrospective study in a cohort of 1,213 hospitalized individuals with COVID-19 and pre-existing T2D indicated that metformin use was significantly associated with a higher incidence of acidosis, particularly in cases with severe COVID-19, but not with 28-day COVID-19-related mortality. Furthermore, metformin use was significantly associated with reduced heart failure and inflammation. Our findings provide clinical evidence in support of continuing metformin treatment in individuals with COVID-19 and pre-existing T2D, but acidosis and kidney function should be carefully monitored in individuals with severe COVID-19.


Assuntos
Acidose/induzido quimicamente , Infecções por Coronavirus/complicações , Diabetes Mellitus Tipo 2/complicações , Metformina/efeitos adversos , Pneumonia Viral/complicações , Acidose Láctica/induzido quimicamente , Idoso , COVID-19 , China/epidemiologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hospitalização , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Estudos Retrospectivos
14.
Lab Chip ; 20(12): 2075-2085, 2020 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-32490853

RESUMO

SARS-CoV-2 is the virus that causes coronavirus disease (COVID-19) which has reached pandemic levels resulting in significant morbidity and mortality affecting every inhabited continent. The large number of patients requiring intensive care threatens to overwhelm healthcare systems globally. Likewise, there is a compelling need for a COVID-19 disease severity test to prioritize care and resources for patients at elevated risk of mortality. Here, an integrated point-of-care COVID-19 Severity Score and clinical decision support system is presented using biomarker measurements of C-reactive protein (CRP), N-terminus pro B type natriuretic peptide (NT-proBNP), myoglobin (MYO), D-dimer, procalcitonin (PCT), creatine kinase-myocardial band (CK-MB), and cardiac troponin I (cTnI). The COVID-19 Severity Score combines multiplex biomarker measurements and risk factors in a statistical learning algorithm to predict mortality. The COVID-19 Severity Score was trained and evaluated using data from 160 hospitalized COVID-19 patients from Wuhan, China. Our analysis finds that COVID-19 Severity Scores were significantly higher for the group that died versus the group that was discharged with median (interquartile range) scores of 59 (40-83) and 9 (6-17), respectively, and area under the curve of 0.94 (95% CI 0.89-0.99). Although this analysis represents patients with cardiac comorbidities (hypertension), the inclusion of biomarkers from other pathophysiologies implicated in COVID-19 (e.g., D-dimer for thrombotic events, CRP for infection or inflammation, and PCT for bacterial co-infection and sepsis) may improve future predictions for a more general population. These promising initial models pave the way for a point-of-care COVID-19 Severity Score system to impact patient care after further validation with externally collected clinical data. Clinical decision support tools for COVID-19 have strong potential to empower healthcare providers to save lives by prioritizing critical care in patients at high risk for adverse outcomes.


Assuntos
Infecções por Coronavirus/diagnóstico , Sistemas de Apoio a Decisões Clínicas/organização & administração , Pneumonia Viral/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Algoritmos , Biomarcadores , COVID-19 , Comorbidade , Infecções por Coronavirus/fisiopatologia , Cuidados Críticos , Humanos , Processamento de Imagem Assistida por Computador , Imunoensaio/métodos , Aprendizado de Máquina , Pandemias , Pneumonia Viral/fisiopatologia , Valor Preditivo dos Testes , Fatores de Risco , Índice de Gravidade de Doença , Software , Resultado do Tratamento
15.
medRxiv ; 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32511607

RESUMO

SARS-CoV-2 is the virus that causes coronavirus disease (COVID-19) which has reached pandemic levels resulting in significant morbidity and mortality affecting every inhabited continent. The large number of patients requiring intensive care threatens to overwhelm healthcare systems globally. Likewise, there is a compelling need for a COVID-19 disease severity test to prioritize care and resources for patients at elevated risk of mortality. Here, an integrated point-of-care COVID-19 Severity Score and clinical decision support system is presented using biomarker measurements of C-reactive protein (CRP), N-terminus pro B type natriuretic peptide (NT-proBNP), myoglobin (MYO), D-dimer, procalcitonin (PCT), creatine kinase-myocardial band (CK-MB), and cardiac troponin I (cTnI). The COVID-19 Severity Score combines multiplex biomarker measurements and risk factors in a statistical learning algorithm to predict mortality. The COVID-19 Severity Score was trained and evaluated using data from 160 hospitalized COVID-19 patients from Wuhan, China. Our analysis finds that COVID-19 Severity Scores were significantly higher for the group that died versus the group that was discharged with median (interquartile range) scores of 59 (40-83) and 9 (6-17), respectively, and area under the curve of 0.94 (95% CI 0.89-0.99). These promising initial models pave the way for a point-of-care COVID-19 Severity Score system to impact patient care after further validation with externally collected clinical data. Clinical decision support tools for COVID-19 have strong potential to empower healthcare providers to save lives by prioritizing critical care in patients at high risk for adverse outcomes.

17.
JAMA Cardiol ; 5(7): 811-818, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32219356

RESUMO

Importance: Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents. Information regarding the impact of cardiovascular complication on fatal outcome is scarce. Objective: To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19. Design, Setting, and Participants: This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020. Analysis began February 25, 2020. Main Outcomes and Measures: Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels. Results: Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died. The mean (SD) age was 58.50 (14.66) years. Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels. The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs. Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]). Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (ß = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (ß = 0.613, P < .001). Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16). During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels. The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13). Conclusions and Relevance: Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable. Myocardial injury is associated with cardiac dysfunction and arrhythmias. Inflammation may be a potential mechanism for myocardial injury. Aggressive treatment may be considered for patients at high risk of myocardial injury.


Assuntos
Betacoronavirus , Doenças Cardiovasculares/epidemiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Adulto , Idoso , COVID-19 , Doenças Cardiovasculares/sangue , China , Infecções por Coronavirus/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Pandemias , Fragmentos de Peptídeos/sangue , Pneumonia Viral/terapia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Taxa de Sobrevida , Troponina T/sangue
18.
Exp Ther Med ; 19(3): 1984, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32104258

RESUMO

[This corrects the article DOI: 10.3892/etm.2019.7161.].

19.
Gene Ther ; 26(7-8): 324-337, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31239537

RESUMO

Advancement of stem cell-based treatment will involve next-generation approaches to enhance therapeutic efficacy which is often modest, particularly in the context of myocardial regenerative therapy. Our group has previously demonstrated the beneficial effect of genetic modification of cardiac stem cells with Pim-1 kinase overexpression to rejuvenate aged cells as well as potentiate myocardial repair. Despite these encouraging findings, concerns were raised regarding potential for oncogenic risk associated with Pim-1 kinase overexpression. Testing of Pim-1 engineered c-kit+ cardiac interstitial cells (cCIC) derived from heart failure patient samples for indices of oncogenic risk was undertaken using multiple assessments including soft agar colony formation, micronucleation, gamma-Histone 2AX foci, and transcriptome profiling. Collectively, findings demonstrate comparable phenotypic and biological properties of cCIC following Pim-1 overexpression compared with using baseline control cells with no evidence for oncogenic phenotype. Using a highly selective and continuous sensor for quantitative assessment of PIM1 kinase activity revealed a sevenfold increase in Pim-1 engineered vs. control cells. Kinase activity profiling using a panel of sensors for other kinases demonstrates elevation of IKKs), AKT/SGK, CDK1-3, p38, and ERK1/2 in addition to Pim-1 consistent with heightened kinase activity correlating with Pim-1 overexpression that may contribute to Pim-1-mediated effects. Enhancement of cellular survival, proliferation, and other beneficial properties to augment stem cell-mediated repair without oncogenic risk is a feasible, logical, and safe approach to improve efficacy and overcome current limitations inherent to cellular adoptive transfer therapeutic interventions.


Assuntos
Carcinogênese/genética , Terapia Genética/efeitos adversos , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-pim-1/genética , Células-Tronco/metabolismo , Transcriptoma , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Feminino , Perfilação da Expressão Gênica , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Testes para Micronúcleos , Miócitos Cardíacos/patologia , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Proteínas Proto-Oncogênicas c-pim-1/metabolismo , Células-Tronco/patologia
20.
J Cardiovasc Electrophysiol ; 30(6): 910-917, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30907035

RESUMO

OBJECTIVE: Early atrial fibrillation (AF) recurrences are common and have been shown to predict AF recurrences late after AF ablation during follow-up. Neiguan point acupuncture has been recognized to be therapeutic in treating AF in clinical practice. METHODS AND RESULTS: Eighty-five patients were enrolled in succession due to persistent AF. All patients were randomized divided into control group and acupuncture group. In the control group (n = 45), amiodarone was orally taken from the first day after pulmonary vein isolation (PVI). In the acupuncture group (n = 40), patients were treated with Neiguan point acupuncture for 7 days and amiodarone was prescribed as same as the control group after PVI. The levels of inflammatory factors were analyzed before operation, 1 week after the operation and 3 months later. After 3 months, the acupuncture group had a lower rate of early recurrences than the control group (5/40 [12.5%] vs 15/45 [33.3%], P = 0.039). The inflammatory factors level in the two groups were significantly increased after ablation. However, compared with the control group, the levels of TNF-α, IL-6, CRP, TGF-ß1, MMP2 in the acupuncture group significantly lower (P < 0.05). In a multivariate analysis, acupuncture was an independent factor associated with a lower rate of early recurrences during the blanking period (odds ratio, 0.17; 95% confidence interval, 0.05-0.63; P = 0.008). CONCLUSION: Neiguan point acupuncture combined with amiodarone is superior to amiodarone alone in reducing early recurrences of patients with persistent AF after PVI. The efficacy of Neiguan acupuncture therapy on the early recurrence is associated with the decreased inflammation factors.


Assuntos
Pontos de Acupuntura , Terapia por Acupuntura , Amiodarona/uso terapêutico , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/terapia , Ablação por Cateter , Frequência Cardíaca/efeitos dos fármacos , Veias Pulmonares/efeitos dos fármacos , Veias Pulmonares/cirurgia , Potenciais de Ação , Terapia por Acupuntura/efeitos adversos , Idoso , Amiodarona/efeitos adversos , Antiarrítmicos/efeitos adversos , Fibrilação Atrial/sangue , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Ablação por Cateter/efeitos adversos , China , Terapia Combinada , Feminino , Humanos , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Veias Pulmonares/fisiopatologia , Recidiva , Método Simples-Cego , Fatores de Tempo , Resultado do Tratamento
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