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BACKGROUND: IL-37 (interleukin-37), a natural suppressor of innate inflammatory and immune responses, is increased in patients with myocardial infarction. Platelets play an important role in the progress of myocardial infarction, but the direct effects of IL-37 on platelet activation and thrombosis, as well as the underlying mechanisms, still remain unclear. METHODS: We evaluated the direct effects of IL-37 on agonists-induced platelet activation and thrombus formation, as well as revealed the underlying mechanisms using platelet-specific IL-1R8 (IL-1 receptor 8)-deficient mice. Using myocardial infarct model, we explored the effects of IL-37 on microvascular obstruction and myocardial injury. RESULTS: IL-37 directly inhibited agonists-induced platelet aggregation, dense granule ATP release, P-selectin exposure, integrin αIIbß3 activation, platelet spreading, and clot retraction. IL-37 inhibited thrombus formation in vivo in a FeCl3-injured mesenteric arteriole thrombosis mouse model and ex vivo in a microfluidic whole-blood perfusion assay. Mechanistic studies using platelet-specific IL-1R8-deficient mice revealed that IL-37 bound to platelet IL-1R8 and IL-18Rα, and IL-1R8 deficiency impaired the inhibitory effects of IL-37 on platelet activation. Using PTEN (phosphatase and tensin homolog)-specific inhibitor and PTEN-deficient platelets, we found that IL-37 combined with IL-1R8 to enhance PTEN activity, inhibit Akt (protein kinase B), mitogen-activated protein kinases, and spleen tyrosine kinase pathways, as well as decrease the generation of reactive oxygen species to regulate platelet activation. Exogenous IL-37 injection suppressed microvascular thrombosis to protect against myocardial injury in wild-type mice but not in platelet-specific IL-1R8-deficient mice after permanent ligation of the left anterior descending coronary. Finally, a negative correlation between plasma IL-37 concentration and platelet aggregation was observed in patients with myocardial infarction. CONCLUSIONS: IL-37 directly attenuated platelet activation, thrombus formation, and myocardial injury via IL-1R8 receptor. Accumulated IL-37 in plasma inhibited platelet activation to ameliorate atherothrombosis and infarction expansion, and thus may have therapeutic advantages as potential antiplatelet drugs.
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Infarto del Miocardio , Trombosis , Animales , Ratones , Plaquetas/metabolismo , Infarto del Miocardio/genética , Infarto del Miocardio/prevención & control , Infarto del Miocardio/metabolismo , Activación Plaquetaria , Agregación Plaquetaria , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/metabolismo , Transducción de Señal , Trombosis/genética , Trombosis/prevención & controlRESUMEN
BACKGROUND: Diabetic cardiomyopathy (DCM), a serious complication of diabetes, leads to structural and functional abnormalities of the heart and ultimately evolves to heart failure. IL-37 exerts a substantial influence on the regulation of inflammation and metabolism. Whether IL-37 is involved in DCM is unknown. METHODS: The plasma samples were collected from healthy controls, diabetic patients and DCM patients, and the level of IL-37 and its relationship with heart function were observed. The changes in cardiac function, myocardial fibrosis and mitochondrial injury in DCM mice with or without IL-37 intervention were investigated in vivo. By an in vitro co-culture approach involving HG challenge of cardiomyocytes and fibroblasts, the interaction carried out by cardiomyocytes on fibroblast profibrotic activation was studied. Finally, the possible interactive mediator between cardiomyocytes and fibroblasts was explored, and the intervention role of IL-37 and its relevant molecular mechanisms. RESULTS: We showed that the level of plasma IL-37 in DCM patients was upregulated compared to that in healthy controls and diabetic patients. Both recombinant IL-37 administration or inducing IL-37 expression alleviated cardiac dysfunction and myocardial fibrosis in DCM mice. Mechanically, hyperglycemia impaired mitochondria through SIRT1/AMPK/PGC1α signaling, resulting in significant cardiomyocyte apoptosis and the release of extracellular vesicles containing mtDNA. Fibroblasts then engulfed these mtDNA-enriched vesicles, thereby activating TLR9 signaling and the cGAS-STING pathway to initiate pro-fibrotic process and adverse remodeling. However, the presence of IL-37 ameliorated mitochondrial injury by preserving the activity of SIRT1-AMPK-PGC1α axis, resulting in a reduction in release of mtDNA-enriched vesicle and ultimately attenuating the progression of DCM. CONCLUSIONS: Collectively, our study demonstrates a protective role of IL-37 in DCM, offering a promising therapeutic agent for this disease.
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ADN Mitocondrial , Cardiomiopatías Diabéticas , Fibrosis , Interleucina-1 , Miocitos Cardíacos , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Apoptosis/efectos de los fármacos , Cardiomiopatías Diabéticas/patología , Cardiomiopatías Diabéticas/metabolismo , Cardiomiopatías Diabéticas/tratamiento farmacológico , ADN Mitocondrial/metabolismo , Fibroblastos/metabolismo , Fibroblastos/efectos de los fármacos , Interleucina-1/metabolismo , Ratones Endogámicos C57BL , Miocardio/patología , Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Transducción de Señal/efectos de los fármacos , Sirtuina 1/metabolismoRESUMEN
It has been reported that vanillin has been intentionally added to enhance the taste and flavor of low-quality vegetable oils. Therefore, it is crucial to investigate the accurate concentrations of vanillin in three types of fragrant vegetable oils commonly consumed in China. In this study, a method has been developed for the quantification of vanillin in commercial fragrant vegetable oils using the stable isotope dilution assay (SIDA) and headspace-solid-phase microextraction (HS-SPME) coupled with gas chromatography/mass spectrometry (GC/MS). The limit of detection (LOD) and limit of quantification (LOQ) of the analyte were determined to be 20 µg kg-1 and 50 µg kg-1, respectively. The validation study demonstrated that the recoveries ranged from 89% to 101%, with intra-day and inter-day precision being less than 7.46%. A survey of 80 commercially available fragrant vegetable oils was performed using the present method. Vanillin was found to be widely present in fragrant vegetable oils, with sesame oils showing the highest average content (842.6 µg kg-1), followed by rapeseed oils (262.1 µg kg-1) and peanut oils (115.0 µg kg-1). The results indicate that the proposed method is a simple, accurate, and eco-friendly approach for determining the presences of vanillin in fragrant vegetable oils.
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Aceites de Plantas , Microextracción en Fase Sólida , Microextracción en Fase Sólida/métodos , Aceites de Plantas/química , Cromatografía de Gases y Espectrometría de Masas/métodos , IsótoposRESUMEN
Background. Far-field electrograms from superior vena cava (SVC) can be present in right superior pulmonary vein (RSPV) after pulmonary vein (PV) isolation. Objectives. To analyze the characteristics of far-field SVC potentials in RSPV after PV isolation and the local anatomy difference between patients with and without the potentials. Methods. Patients undergoing PV isolation were retrospectively reviewed, contrast-enhanced computed tomography (CT) was performed before procedure for observing the anatomical relationship between RSPV and SVC. The prevalence and characteristics of far-field SVC electrograms were described and compared to far-field left atrial potentials at the nearest point along the linear ablation lesion. The anatomical proximity of RSPV and SVC on a 2-dimensional horizontal CT view was compared between patients with and without far-field SVC potentials. Results. Far-field SVC electrograms were observed in 35/92(38%) patients with an amplitude of 0.24 ± 0.11 mV and a major deflection slope of 0.051 ± 0.036 mV, both significantly higher than far-field left atrial electrograms (p < .001). In patients with far-field SVC electrograms, 83% had connected RSPV-SVC, defined as distance between RSPV and SVC endocardium less than 3 mm at the layer of RSPV ostium roof, while in patients without far-field SVC electrograms, 70% had disconnected RSPV-SVC. Conclusions. Far-field SVC electrograms appeared in RSPV had a prevalence higher than previously reported and a sharper major deflection compared to far-field left atrial electrograms. Connected RSPV-SVC on CT was associated with the presence of far-field SVC electrograms.
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Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/cirugía , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos , Humanos , Venas Pulmonares/diagnóstico por imagen , Venas Pulmonares/cirugía , Estudios Retrospectivos , Vena Cava Superior/diagnóstico por imagen , Vena Cava Superior/cirugíaRESUMEN
BACKGROUND: Three dimensional speckle tracking echocardiography (3D STE) is a novel technique combining 3D echocardiography and speckle tracking analysis. 3D STE software dedicated to the left atrium (LA) was recently available. Our study aimed to assess (1) atrial fibrillation (AF) related LA morpho-functional remodeling using 3D STE and (2) value of LA function parameters in identifying paroxysmal AF (PAF). METHODS: One hundred thirty-nine PAF, 109 persistent AF (Per-AF) and 59 non-AF subjects underwent 3D STE. LA phasic volumes and total LA emptying fraction (LAEF) were obtained and used to calculate passive (pLAEF) and active LA emptying fraction (aLAEF) based on atrial contraction. LA longitudinal and circumferential strain representing reservoir (LASr/LASrc), conduit (LAScd/LAScdc) and pump (LASct/LASctc) function were also assessed. RESULTS: 3D STE was found to have good reproducibility. Increase of LA volumes and decrease of parameters representing LA reservoir and pump function were independently associated with AF as well as AF burden. The correlations between LA emptying fraction and LA circumferential strain representing the same function were always stronger than those with LA longitudinal strain (p < 0.001). Minimal LA volume, LAEF, aLAEF, LASrc and LASctc can be used to accurately differentiate PAF from non-AF subjects (AUC > 0.8) with great sensitivity and specificity. CONCLUSIONS: Assessing LA remodeling in AF using 3D STE was feasible. AF and AF burden were independently associated with LA enlargement and impairment of reservoir and pump function but not conduit function. LA function parameters can indicate underlying PAF and thus can guide AF screening strategy.
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Fibrilación Atrial , Remodelación Atrial , Fibrilación Atrial/diagnóstico , Función del Atrio Izquierdo , Ecocardiografía/métodos , Humanos , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Hypertension is highly prevalent and is one of the modifiable risk factors for cardiovascular outcomes. Isolated diastolic hypertension (IDH), however, tends to be ignored due to insufficient recognition. We sought to depict the clinical manifestation of IDH and isolated systolic hypertension (ISH) to find a more efficient way to improve the management. METHODS: Patients with primary hypertension aged over 18 years were investigated from all over the country using convenience sampling during 2017-2019. IDH was defined as systolic blood pressure (SBP) < 140 mmHg and diastolic blood pressure (DBP) ≥90 mmHg. ISH was defined as SBP ≥ 140 mmHg and DBP < 90 mmHg. RESULTS: A total of 8548 patients were screened, and 8475 participants were included. The average age was 63.67 ± 12.78 years, and males accounted for 54.4%. Among them, 361 (4.3%) had IDH, and 2096 had ISH (24.7%). Patients with IDH (54.84 ± 13.21 years) were much younger. Aging turned out to be negatively associated with IDH but positively associated with ISH. Multivariate logistic regression analysis showed BMI was a significant risk factor for IDH (OR 1.30, 95%CI 1.05-1.61, p = 0.018), but not for ISH (OR 1.05, 95%CI 0.95-1.16, p = 0.358). Moreover, smoking was significantly associated with IDH (OR 1.36, 95%CI 1.04-1.78, p = 0.026) but not with ISH (OR 1.04, 95%CI 0.90-1.21, p = 0.653). CONCLUSIONS: Patients with IDH were much younger, and the prevalence decreased with aging. BMI and smoking were remarkably associated with IDH rather than ISH. Keeping fit and giving up smoking might be particularly efficient in the management of young patients with IDH. TRIAL REGISTRATION: NCT03862183 , retrospectively registered on March 5, 2019.
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Hipertensión , Adulto , Anciano , Presión Sanguínea , Humanos , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Factores de RiesgoRESUMEN
Under the condition of lipopolysaccharide (LPS)/interferon (IFN)-γ activation, macrophage metabolism is converted from oxidative phosphorylation to glycolysis. In the present work, we analysed whether glycolysis could affect interleukin (IL)-1ß expression through altering histone acetylation levels in mouse bone marrow-derived macrophages. Immunocytochemistry and Western blot analysis are used to characterize histone acetylation in macrophages stimulated by LPS/IFN-γ. Real-time polymerase chain reaction and enzyme-linked immunosorbent assay were used to determine IL-1ß production. The metabolism of macrophages was monitored in real-time by the Seahorse test. Our results showed that glycolytic metabolism could enhance histone acetylation and promote IL-1ß production in LPS/IFN-γ-activated macrophages. Moreover, increased production of IL-1ß by glycolysis was mediated through enhanced H3K9 acetylation. Importantly, it was found that a high dose of histone deacetylase inhibitor could also significantly increase the expression of IL-1ß in the absence of glycolytic metabolism. In conclusion, this study demonstrates that glycolytic metabolism could regulate IL-1ß expression by increasing histone acetylation levels in LPS/IFN-γ-stimulated macrophages.
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Histonas/metabolismo , Interleucina-1beta/metabolismo , Activación de Macrófagos , Macrófagos/inmunología , Acetilación , Animales , Células Cultivadas , Glucólisis/inmunología , Interferón gamma/inmunología , Lipopolisacáridos/inmunología , Macrófagos/metabolismo , Ratones , Cultivo Primario de Células , Proteínas Recombinantes/inmunologíaRESUMEN
Recent studies have shown that TRPA1, a nonselective cation channel with high permeability to calcium, is expressed in many tissues of the cardiovascular system and is involved in the pathogenesis of many cardiovascular diseases. However, the role of TRPA1 in cardiac repair after myocardial infarction (MI) has not been clearly defined. The aim of this study was to confirm whether inhibition of TRPA1 could attenuate MI-induced cardiac ischemia injury. The C57BL/6 mice were subjected to ligation of the left anterior descending coronary artery and treated with TRPA1-specific inhibitor HC-030031 (HC) for 4 weeks. Echocardiography was performed to assess cardiac function. The results showed that HC significantly attenuated MI-induced cardiac dysfunction 4 weeks after MI. Similarly, HC reduced cardiac fibrosis and cell apoptosis after MI and significantly increased angiogenesis in the border zone of the infarct. In vitro, we found that HC promoted the proliferation and migration of human umbilical vein endothelial cells (HUVECs). Importantly, HC treatment decreased phosphatase and tensin homolog expression and augmented the expression of phosphorylated Akt in the myocardium post MI and HUVECs. However, treatment of HUVECs with a PI3K inhibitor, LY294002, before HC administration almost completely abolished HC-induced migration in HUVECs. In conclusion, we demonstrate that the inhibition of TRPA1 promotes angiogenesis after MI, thereby alleviating myocardial ischemia injury via mechanisms involving inhibition of phosphatase and tensin homolog expression and subsequent activation of the PI3K/Akt signaling.
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Acetanilidas/farmacología , Infarto del Miocardio/tratamiento farmacológico , Miocitos Cardíacos/efectos de los fármacos , Purinas/farmacología , Canal Catiónico TRPA1/antagonistas & inhibidores , Función Ventricular Izquierda/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Modelos Animales de Enfermedad , Fibrosis , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Ratones Endogámicos C57BL , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Neovascularización Fisiológica , Fosfohidrolasa PTEN/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Canal Catiónico TRPA1/metabolismoRESUMEN
BACKGROUND: Autophagy plays a crucial role in the pathological process of cardiovascular diseases. However, little is known about the pathological mechanism underlying autophagy regulation in dilated cardiomyopathy (DCM). METHODS: We explored whether up-regulating autophagy could improve cardiac function in mice with experimental DCM through the mTOR-4EBP1 pathway. Animal model of DCM was established in BALB/c mice by immunization with porcine cardiac myosin. Both up- or down-regulation of autophagy were studied by administration of rapamycin or 3-MA in parallel. Morphology, Western blotting, and echocardiography were applied to confirm the pathological mechanisms. RESULTS: Autophagy was activated and autophagosomes were significantly increased in the rapamycin group. The collagen volume fraction (CVF) was decreased in the rapamycin group compared with the DCM group (9.21 ± 0.82% vs 14.38 ± 1.24%, P < 0.01). The expression of p-mTOR and p-4EBP1 were significantly decreased in rapamycin-induced autophagy activation, while the levels were increased by down-regulating autophagy with 3-MA. In the rapamycin group, the LVEF and FS were significantly increased compared with the DCM group (54.12 ± 6.48% vs 45.29 ± 6.68%, P < 0.01; 26.89 ± 4.04% vs 22.17 ± 2.82%, P < 0.05). As the inhibitor of autophagy, 3-MA aggravated the progress of maladaptive cardiac remodeling and declined cardiac function in DCM mice. CONCLUSIONS: The study indicated a possible mechanism for improving cardiac function in mice with experimental DCM by up-regulating autophagy via the mTOR-4EBP1 pathway, which could be a promising therapeutic strategy for DCM.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Autofagia/efectos de los fármacos , Cardiomiopatía Dilatada/tratamiento farmacológico , Proteínas de Ciclo Celular/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Sirolimus/farmacología , Serina-Treonina Quinasas TOR/metabolismo , Función Ventricular Izquierda/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , Animales , Autofagosomas/efectos de los fármacos , Autofagosomas/enzimología , Autofagosomas/patología , Cardiomiopatía Dilatada/enzimología , Cardiomiopatía Dilatada/patología , Cardiomiopatía Dilatada/fisiopatología , Modelos Animales de Enfermedad , Fibrosis , Masculino , Ratones Endogámicos BALB C , Miocitos Cardíacos/enzimología , Miocitos Cardíacos/patología , Recuperación de la Función , Transducción de SeñalRESUMEN
Patients with atrial fibrillation (AF) are associated with increased thrombotic events. Our previous case-control study showed low-density lipoprotein cholesterol (LDL-C) was an independent predictor of ischemic stroke in AF patients. To investigate the risks of thrombosis in relation to LDL-C among AF patients at different stroke risks by long-time follow-up. Atrial fibrillation patients without history of thrombosis enrolled from five hospitals were classified into low-risk (LR) and high-risk (HR) group according to CHA2DS2VASc score and followed up with a median period of 26 months. Univariate and multivariate logistic regression analysis were performed in each group. The best cut-off value calculated by receiver operating characteristic (ROC) analysis was used to divide patients into low LDL-C (L-LDL) and high LDL-C (H-LDL) subgroups. Propensity score matching (PSM) and inverse probability of treatment weighted (IPTW) were utilized in both subgroups, after which Kaplan-Meier curves for thrombosis were performed. Univariate and multivariate analysis showed LDL-C was significantly related to thrombosis in LR, but less significantly in HR group. The best cut-off value was 2.155 mmol/L in LR and 2.795 mmol/L in HR group. Lower LDL-C was associated with decreased thrombosis in both groups by PSM and IPTW. Kaplan-Meier curves displayed that H-LDL subgroup was at higher thrombosis risk with significant difference at 24th month in LR patients. LDL-C independently predicts thrombosis with different cut-off values in AF patients at different risks. A stricter control of LDL-C level is necessary for thrombosis reduction in patients with lower score.
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Fibrilación Atrial , LDL-Colesterol/sangre , Accidente Cerebrovascular Isquémico , Medición de Riesgo/métodos , Trombosis , Fibrilación Atrial/sangre , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , China/epidemiología , Femenino , Humanos , Accidente Cerebrovascular Isquémico/etiología , Accidente Cerebrovascular Isquémico/prevención & control , Estimación de Kaplan-Meier , Masculino , Registros Médicos/estadística & datos numéricos , Valor Predictivo de las Pruebas , Pronóstico , Factores de Riesgo , Trombosis/sangre , Trombosis/epidemiología , Trombosis/prevención & control , TiempoRESUMEN
Multiple studies demonstrated that early growth response factor 1 (EGR1) induces myocardial damage after acute myocardial infarction (AMI). Recent evidence indicates that microRNAs (miRNA) play an important role in exosome-mediated cardioprotection after AMI. Bioinformatics analysis has shown that miR-146a can regulate the expression of EGR1, so the aim of this study was to determine if miR-146a plays a role in exosome-mediated cardioprotection by regulation of EGR1 after AMI. Exosomes were isolated from wild- or miR-146a-modified adipose-derived stem cells (ADSCs), and the therapeutic effect of exosomes was assessed in an AMI model in rats and hypoxic-induced H9c2 model cells. The results showed that miR-146a containing exosomes had more effect than the exosome treatment group on the suppression of AMI-induced apoptosis, inflammatory response, and fibrosis in an AMI rat model. Both in vivo and in vitro experiments found that miR-146a interacted with the 3'-untranslated region of EGR1 and suppressed posttranscriptional EGR1 expression, which was confirmed by the luciferase reporter assay. We also found that suppressed EGR1 expression reversed AMI or hypoxia-induced TLR4/NFκB signal activation, which played an important role in the promotion of myocardial cell apoptosis, inflammatory response, and fibrosis. Taken together, these findings suggested that exosomes derived from miR-146a-modified ADSCs attenuated AMI-induced myocardial damage via downregulation of EGR1.
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Regulación hacia Abajo/genética , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Exosomas/metabolismo , Células Madre Mesenquimatosas/citología , MicroARNs/genética , Infarto del Miocardio/metabolismo , Regiones no Traducidas 3'/genética , Animales , Apoptosis/genética , Hipoxia de la Célula , Línea Celular , Modelos Animales de Enfermedad , Fibrosis/metabolismo , Masculino , Miocardio/metabolismo , FN-kappa B/metabolismo , Ratas , Ratas Sprague-Dawley , Receptor Toll-Like 4/metabolismo , TransfecciónRESUMEN
Oxidized low-density lipoprotein (ox-LDL)-induced oxidative stress and apoptosis are considered as a critical contributor to atherosclerosis. MicroRNAs (miRNAs) have been reported versatile functions in all biological processes via directly suppressing target messenger RNA at a posttranscriptional level. Although miRNA-221 has been implied to be involved in the regulation of atherosclerosis, the underlying mechanism remains unclear. Here, we showed that ox-LDL treatment remarkably suppressed the expression of miR-221-3p in a concentration-dependent and time-dependent manner. Transfection of miR-221-3p mimic significantly reduced the foam cell formation and expression of lipid biomarkers, while transfection of the miR-221-3p inhibitor showed completely opposite effects. Moreover, miR-221-3p was also found to inhibit the process of cell apoptosis in macrophages. A disintegrin and metalloprotease-22 (ADAM22) is predicted as a direct target of miR-221-3p, and silencing AMAM22 resulted in a reduced foam cell formation and cell apoptosis. Furthermore, silencing AMAM22 restored the stimulatory effect of the miR-221-3p inhibitor in ox-LDL-induced foam cell formation and apoptosis. These findings suggest that miR-221-3p inhibits ox-LDL and apoptosis via directly targeting ADAM22.
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Proteínas ADAM/genética , Células Espumosas/citología , Lipoproteínas LDL/farmacología , MicroARNs/genética , Proteínas del Tejido Nervioso/genética , Regiones no Traducidas 3' , Proteínas ADAM/metabolismo , Animales , Apoptosis/efectos de los fármacos , Regulación hacia Abajo , Células Espumosas/efectos de los fármacos , Células Espumosas/metabolismo , Regulación de la Expresión Génica , Ratones , MicroARNs/farmacología , Proteínas del Tejido Nervioso/metabolismo , Estrés Oxidativo/efectos de los fármacos , Células RAW 264.7RESUMEN
BACKGROUND: With the rising utilization of cardiovascular implantable electronic devices (CIEDs), infections secondary to device implantation are increasingly encountered. Staphylococcus aureus and coagulase-negative staphylococci are usually the predominant causative organisms. A CIED infection due to non-tuberculous mycobacteria (NTM) is extremely rare. CASE PRESENTATION: A 68-year-old man was admitted to our hospital with a history of pain and swelling at his cardiac resynchronization therapy-defibrillator (CRT-D) pocket site, for 4 days. The CRT-D had been implanted 2 weeks prior. The exudate smear was positive for acid-fast bacilli and culture results revealed rapidly growing nontuberculous mycobacteria (RGM). After an urgent removal of the device followed by 1 year of antibiotic treatment, the patient was completely cured. A new device was finally implanted, 3 years later. CONCLUSIONS: Infections caused by nontuberculous mycobacteria following the implantation of cardiac devices are very rare. The typical manifestations of post-implantation CIED infections caused by RGMs include an early onset, with local redness, swelling, and spontaneous drainage. Systemic symptoms such as fever, chills, and fatigue are absent. Mycobacterium fortuitum is the most common species of RGM implicated in CIED infections, the manifestations of which usually appear within several weeks of the implantation procedure. An urgent removal of the device and appropriate antibiotic therapy are essential therapeutic measures. This is the first such reported case, in which the patient has been re-implanted with another device at the same site, after achieving a complete cure. We followed-up the patient for an additional 3 years and observed that the patient remained free of infection. Our case report shows that though an RGM infection is rare and difficult to treat, it can be completely cured. In addition, we demonstrated that it is subsequently possible to safely re-implant a CIED for the patient, at the same site.
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Dispositivos de Terapia de Resincronización Cardíaca/efectos adversos , Terapia de Resincronización Cardíaca , Infecciones por Mycobacterium no Tuberculosas/microbiología , Mycobacterium fortuitum/aislamiento & purificación , Anciano , Antibacterianos/administración & dosificación , Remoción de Dispositivos , Humanos , Masculino , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/terapia , Resultado del TratamientoRESUMEN
BACKGROUND: Constrictive pericarditis (CP) is defined as impaired diastolic cardiac function caused by a calcified and thickened pericardium. We assessed the clinical characteristics and time to diagnosis, as well as patient prognosis after pericardiectomy. Methods: We analyzed the records of 36 CP patients who underwent pericardiectomy at Huashan Hospital, China, between 2012 and 2015. Clinical manifestations, length of time to diagnosis, laboratory parameters, and diagnostic imaging results were examined. All patients underwent pericardiectomy, and were assessed post-operatively for quality of life and improvement of cardiac function using the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Results: All patients displayed shortness of breath and polyserous effusion, as well as elevated pro B-type natriuretic peptide and thickened pericardium. Mean time between onset of symptoms and a definitive diagnosis of CP was 9.5 ± 2.1 months. Pericardiectomy was performed within one week of diagnosis. Mean central venous pressure decreased from a pre-operative 19.92 ± 6.6 mmHg to a post-operative 8.5 ± 2.7 mmHg. Within 1.5 ± 0.7 years of surgery, all patients maintained good quality of life and cardiac function, which resulted in a mean score of 0.9 ± 0.6 on the MLHFQ. Conclusion: A definitive diagnosis of CP is usually made long after the onset of symptoms. Early detection and diagnosis by echocardiography with elevated central venous pressure and early treatment by surgery are key to an improved prognosis and resumption of good cardiac function.
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Presión Venosa Central/fisiología , Ecocardiografía/métodos , Pericardiectomía/métodos , Pericarditis Constrictiva/diagnóstico , Pericardio/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adulto , Femenino , Humanos , Masculino , Pericarditis Constrictiva/fisiopatología , Pericarditis Constrictiva/cirugía , Pericardio/cirugía , Pronóstico , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
BACKGROUND/AIMS: Mitochondrial DNA (mtDNA), acting as a newly found 'danger-associated molecular patterns' (DAMPs), is released into circulation upon tissue injury and performs as a considerable activator of inflammation and immune response. However, the role of circulating mtDNA in experimental autoimmune myocarditis (EAM) as well as Toll like receptor4 (TLR4) mediated cardiac inflammation and injury remains unknown. METHODS: A model of EAM was established in BALB/c mice by immunization with porcine cardiac myosin. Lipopolysaccharide (LPS) was used to stimulate TLR4 activation in EAM mice and H9C2 cells. RESULTS: LPS stimulation significantly aggravated cardiac inflammation and tissue injury in EAM, as demonstrated by increased myocardium inflammatory cell infiltration, and up-regulated inflammatory cytokines and troponin I(TnI) level in serum. Circulating mtDNA level was increased in EAM and TLR4 activation led to a greater elevation, which may be related to Reactive oxygen species (ROS) stress involved mtDNA damage characterized by reduced mtDNA copy number in myocardium tissue. In addition, the expression of Toll like receptor9 (TLR9), a ligand of mtDNA, was significantly up-regulated in the myocardium of EAM and EAM LPS group; meanwhile, TLR9 inhibition by ODN 2088 caused an inhibited apoptosis in LPS treated H9C2 cells. Moreover, in EAM and EAM LPS group, simultaneously giving ODN 2088 treatment significantly ameliorated cardiac inflammation and tissue injury compared with untreated group. CONCLUSION: Increased circulating mtDNA combined with upregulated TLR9 expression may corporately play a role in EAM as well as TLR4 activation mediated cardiac inflammation and injury.
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Enfermedades Autoinmunes/sangre , ADN Mitocondrial/sangre , Miocarditis/sangre , Receptor Toll-Like 4/biosíntesis , Receptor Toll-Like 9/biosíntesis , Animales , Apoptosis/genética , Enfermedades Autoinmunes/inducido químicamente , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/patología , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Lesiones Cardíacas/sangre , Lesiones Cardíacas/genética , Lesiones Cardíacas/patología , Humanos , Inflamación/sangre , Inflamación/genética , Inflamación/patología , Lipopolisacáridos/toxicidad , Ratones , Miocarditis/inducido químicamente , Miocarditis/genética , Miocarditis/patología , Miocardio/metabolismo , Miocardio/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Especies Reactivas de Oxígeno/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 9/genética , Troponina I/sangreRESUMEN
For the patients with essential thrombocythemia (ET), systemic thrombosis presents as one of the most dangerous complications. It's been widely accepted that acute coronary syndrome (ACS) is a kind of thrombotic diseases. However, there are very few case reports about ET first presenting as ACS. For some patients diagnosed as ACS, but without markedly elevated platelet, underlying ET was missed. And there are some controversies in the principles and target of treatment in those patients. We reported three cases of ACS, in which the patients who did not have common risk factors for coronary artery diseases and presented only mild atherosclerotic stenosis during coronary angiography, one of which had recurrent coronary artery thrombosis. Noticing their elevated blood platelet level and characteristics in angiography, diagnosis of ET was made according to bone marrow morphology and genetic tests. Although they had only mild thrombocytosis, we applied intensive treatment with dual anti-platelet therapy combined with cytoreduction in addition to early coronary intervention, having satisfying outcomes. During the diagnosis and treatment of ACS, if patients present thrombocytosis, but lack common coronary disease risk factors and thrombotic coronary artery occlusion, cardiologists should search for possible ET as an underlying cause of thrombotic coronary event. All those patients were high-risk according to ET risk stratification. Treatment of cytoreduction in combination with anti-thrombosis therapy and revascularization are beneficial. Treatment aims at the target of complete response with platelet count below 400 × 109/L.
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Síndrome Coronario Agudo , Angiografía Coronaria , Trombocitemia Esencial , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/diagnóstico por imagen , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Trombocitemia Esencial/sangre , Trombocitemia Esencial/diagnóstico , Trombocitemia Esencial/diagnóstico por imagen , Trombocitemia Esencial/terapiaRESUMEN
BACKGROUND: Foam cells play a key role in the occurrence and pathogenesis of atherosclerosis. Its formation starts with the ingestion of oxidized low-density lipoprotein (oxLDL). The process is associated with Ras related protein in brain 5 (Rab5) which plays a critical role in regulating endocytosis and early endosomal trafficking. Base on this, we presumed that Rab5 might participate in the maturation of foam cell. The aim of this study is to investigate the effect of Rab5 on macrophage cholesterol during the evolvement of macrophage when induced by oxLDL to the formation of foam cell. METHODS: Immunohistochemistry was performed to analyze the distribution of macrophages and Rab5 in atherosclerotic plaque. RNA inteference study and transfection of inactive mutant (GFP-Rab5-S34N) and active mutant (GFP-Rab5-Q79L) in U937-derived macrophage were utilized to investigate the impact of Rab5 on the process of macrophage cholesterol, which could be detected by oil red O staining, determination of intracellular lipid content, filipin staining, nile red staining and the costaining of early endosome antigen-1 (EEA-1) and 1,1'-dioctadecyl-3,3,3',3'-tetramethylin dicarbocyanine (Dil)-labelled oxLDL (Dil-oxLDL). RESULTS: Rab5 was found abundantly localized in macrophage rich areas of human atherosclerotic lesions. On the foam cell study, the expression of Rab5 was increased after the incubation of oxLDL. The inteference study indicated the depletion of Rab5 led to the decreases of oil red O staining areas, total cholesterol and cholesterol esters in U937-derived marophages. Moreover, the fluorescence intensity of filipin and nile red staining were lower in GFP-Rab5-S34N as compared with GFP-Rab5-Q79L. The confocal study demonstrated less Dil-oxLDL was internalized in GFP-Rab5-S34N as compared with GFP-Rab5-Q79L; the result showed also the decrease in colocalization of internalized Dil-oxLDL and EEA-1 for GFP-Rab5-S34N as compared with GFP-Rab5-Q79L. CONCLUSIONS: Rab5 plays an important role in modulating the intracellular cholesterol of macrophages and consequently mediating the formation of foam cells.
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Células Espumosas/fisiología , Macrófagos/citología , Placa Aterosclerótica/patología , Proteínas de Unión al GTP rab5/metabolismo , Línea Celular , Colesterol/metabolismo , Células Espumosas/citología , Regulación de la Expresión Génica , Guanosina Difosfato/metabolismo , Humanos , Lipoproteínas LDL/metabolismo , Macrófagos/patología , Mutación , Placa Aterosclerótica/metabolismo , Proteínas de Unión al GTP rab5/genéticaRESUMEN
Preexisting renal impairment and the amount of contrast media are the most important risk factors for contrast-induced acute kidney injury (CI-AKI). We aimed to investigate whether the product of contrast medium volume and urinary albumin/creatinine ratio (CMV × UACR) would be a better predictor of CI-AKI in patients undergoing nonemergency coronary interventions. This was a prospective single-center observational study, and 912 consecutive patients who were exposed to contrast media during coronary interventions were investigated prospectively. CI-AKI is defined as a 44.2 µmol/L rise in serum creatinine or a 25% increase, assessed within 48 h after administration of contrast media in the absence of other causes. Fifty patients (5.48%) developed CI-AKI. The urinary albumin/creatinine ratio (UACR) (OR = 1.002, 95% CI = 1.000-1.003, p = .012) and contrast medium volume (CMV) (OR = 1.008, 95% CI = 1.001-1.014, p = .017) were independent risk factors for the development of CI-AKI. The area under the ROC curve of CMV, UACR and CMV × UACR were 0.662 (95% CI = 0.584-0.741, p < .001), 0.761 (95% CI = 0.674-0.847, p < .001) and 0.808 (95% CI = 0.747-0.896, p < .001), respectively. The cutoff value of CMV × UACR to predict CI-AKI was 1186.2, with 80.0% sensitivity and 62.2% specificity. The product of CMV and UACR (CMV × UACR) might be a predictor of CI-AKI in patients undergoing nonemergency coronary interventions, which was superior to CMV or UACR alone.
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Lesión Renal Aguda/orina , Albuminuria/orina , Medios de Contraste/efectos adversos , Angiografía Coronaria/efectos adversos , Creatinina/orina , Intervención Coronaria Percutánea/efectos adversos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/diagnóstico , Anciano , Biomarcadores/orina , Medios de Contraste/administración & dosificación , Creatinina/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: 3-monochloro-1, 2-propanediol fatty acid esters (3-MCPDEs) comprise a group of food toxicants formed during food processing. 3-MCPDEs have received increasing attention concerning their potential negative effects on human health. However, reports on the toxicity of 3-MCPD esters are still limited. To determine the effects of fatty acid substitutions on the toxicity of their esters, 1-stearic, 1-oleic, 1-linoleic, 1-linoleic-2-palmitic and 1-palmitic-2-linoleic acid esters of 3-MCPD were synthesized and evaluated with respect to their acute oral toxicities in Swiss mice. RESULTS: 3-MCPDEs were obtained through the reaction of 3-MCPD and fatty acid chlorides, and their purities and structures were characterized by ultraperformance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS), infrared, 1 H and 13 C spectroscopic analyses. Medial lethal doses of 1-stearic, 1-oleic, 1-linoleic, 1-linoleic-2-palmitic and 1-palmitic-2-linoleic acid esters were 2973.8, 2081.4, 2016.3, 5000 and > 5000 mg kg-1 body weight. For the first time, 3-MCPDEs were observed for their toxic effects in the thymus and lung. In addition, major histopathological changes, as well as blood urea nitrogen and creatinine, were examined for mice fed the five 3-MCPDEs. CONCLUSION: The results from the present study suggest that the degree of unsaturation, chain length, number of substitution and relative substitution locations of fatty acids might alter the toxicity of 3-MCPDEs. © 2016 Society of Chemical Industry.
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Diglicéridos/toxicidad , Contaminación de Alimentos , Hidrocarburos Clorados/toxicidad , Hígado/efectos de los fármacos , Monoglicéridos/toxicidad , Síndromes de Neurotoxicidad/etiología , Timo/efectos de los fármacos , Animales , Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/patología , Diglicéridos/síntesis química , Diglicéridos/química , Femenino , Manipulación de Alimentos , Hidrocarburos Clorados/síntesis química , Hidrocarburos Clorados/química , Dosificación Letal Mediana , Hígado/patología , Masculino , Ratones , Estructura Molecular , Monoglicéridos/síntesis química , Monoglicéridos/química , Neuronas/efectos de los fármacos , Neuronas/patología , Síndromes de Neurotoxicidad/sangre , Síndromes de Neurotoxicidad/patología , Tamaño de los Órganos/efectos de los fármacos , Distribución Aleatoria , Relación Estructura-Actividad , Timo/patología , Pruebas de Toxicidad AgudaRESUMEN
The present study was conducted to isolate and characterize anti-inflammatory peptides from whey protein hydrolysates using alcalase. Nine subfractions were obtained after sequential purification by ultrafiltration, Sephadex G-25 gel (GE Healthcare, Uppsala, Sweden) filtration chromatography, and preparative HPLC. Among them, subfraction F4e showed the strongest inhibitory activity on interleukin-1ß (IL-1ß), cyclooxygenase-2, and tumor necrosis factor-α (TNF-α) mRNA expression in lipopolysaccharide-induced RAW 264.7 mouse macrophages. Eight peptides, including 2 new peptides-Asp-Tyr-Lys-Lys-Tyr (DYKKY) and Asp-Gln-Trp-Leu (DQWL)-were identified from subfractions F4c and F4e, respectively, using ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Peptide DQWL showed the strongest inhibitory ability on IL-1ß, cyclooxygenase-2, and TNF-α mRNA expression and production of IL-1ß and TNF-α proteins at concentrations of 10 and 100µg/mL, respectively. Additionally, DQWL treatment significantly inhibited nuclear factor-κB activation by suppressing nuclear translocation of nuclear factor-κB p65 and blocking inhibitor κB kinase phosphorylation and inhibitor κB degradation together with p38 mitogen-activated protein kinase activation. Our study suggests that peptide DQWL has anti-inflammatory potential; further confirmation using an in vivo model is needed.