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Aims: To investigate the effects of M-CSF on myocardial injury in mice after MI by regulating different types of cardiac macrophages through the P2X7R/NLRP3/IL-1ß signal pathway. Methods: A total of 60 C57BL/6J WT mice were used, with the Sham Group subjected to ligation without ligation through the LAD, the MI model was prepared by ligation of the LAD in the MC Group and MM Group, with the M-CSF reagent (500 µg/kg/d) being given an intraperitoneal injection for the first 5 days after surgery in the MM Group. All mice were fed in a barrier environment for 1 week. After the study, myocardial tissues were collected and IL-4, IL-6, IL-10, TNF-α, MCP-1, IFN-α, ANP, BNP, ß-MHC, Collage I, Collage III, P2X7R, NLRP3, IL-1ß, Bax, Caspase 3, C-Casp 3, Bcl-2, M1/2 macrophage, the apoptosis of cardiomyocytes, and the collagen deposition were detected. Results: The inflammatory response was significantly lower in the MM Group, the cardiomyocyte apoptosis, fibrosis, and hypertrophy were inhibited compared to the MC Group, and the levels of P2X7R, NLRP3, and IL-1ß were also statistically lower in the MM Group. Additionally, the expression of M2 macrophages increased in the MM Group while the M1 macrophages statistically decreased compared to the MC Group. Conclusion: M-CSF can significantly increase the expression of M2 macrophage and reduce the level of M1 macrophage by inhibiting the levels of NLRP3/IL-1ß-related proteins, thereby inhibiting inflammation, ameliorating reducing myocardial hypertrophy, apoptosis, and fibrosis, improve myocardial injury in mice after MI.
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The aim was to investigate the role of the α7nAChR-mediated cholinergic anti-inflammatory pathway in vagal nerve regulated atrial fibrillation (AF).18 beagles (standard dogs for testing) were used in this study, and the effective refractory period (ERP) of atrium and pulmonary veins and AF inducibility were measured hourly during rapid atrial pacing at 800 beats/minute for 6 hours in all beagles. After cessation of 3 hours of RAP, the low-level vagal nerve stimulation (LL-VNS) group (n = 6) was given LL-VNS and injection of salinne (0.5 mL/GP) into four GPs, the methyllycaconitine (MLA, the antagonist of α7nAChR) group (n = 6) was given LL-VNS and injection of MLA into four GPs, and the Control group (n = 6) was given saline into four GPs and the right cervical vagal nerve was exposed without stimulation. Then, the levels of the tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), acetylcholine (ACh), STAT3, and NF-κB proteins were measured. During the first 3 hours of RAP, the ERPs gradually decreased while the dispersion of ERPs (dERPs) and AF inducibility gradually increased in all three groups. During the last 3 hours of 6 hours' RAP in this study, the ERPs in the LL-VNS group were higher, while the dERPs and AF inducibility were significantly lower when compared with the Control and MLA groups at the same time points. The levels of ACh in the serum and atrium in the LL-VNS and MLA groups were higher than in the Control group, and the levels of TNF-α and IL-6 were higher in the Control and MLA groups than in the LL-VNS group. The concentrations of STAT3 in RA and LA tissues were higher in the LL-VNS group while those of NF-κB were lower.In conclusion, the cholinergic anti-inflammatory pathway mediated by α7nACh plays an important role in low-level vagal nerve-regulated AF.
Assuntos
Aconitina/análogos & derivados , Fibrilação Atrial/fisiopatologia , Neuroimunomodulação/efeitos dos fármacos , Nervo Vago/efeitos dos fármacos , Receptor Nicotínico de Acetilcolina alfa7/antagonistas & inibidores , Acetilcolina/sangue , Aconitina/administração & dosagem , Aconitina/farmacologia , Animais , Estimulação Cardíaca Artificial/efeitos adversos , Estimulação Cardíaca Artificial/métodos , Estudos de Casos e Controles , Modelos Animais de Doenças , Cães , Átrios do Coração/inervação , Átrios do Coração/fisiopatologia , Interleucina-6/sangue , NF-kappa B/sangue , Antagonistas Nicotínicos/administração & dosagem , Antagonistas Nicotínicos/farmacologia , Veias Pulmonares/inervação , Veias Pulmonares/fisiopatologia , Período Refratário Eletrofisiológico/efeitos dos fármacos , Fator de Transcrição STAT3/sangue , Fator de Necrose Tumoral alfa/sangue , Estimulação do Nervo Vago/efeitos adversos , Estimulação do Nervo Vago/métodosRESUMO
The three typical carbon enterprises in Zhengzhou were selected as research targets, and the emission characteristics of volatile organic compounds (VOCs) and their ozone formation potential (OFP) in different functional areas were studied. The US Environmental Protection Agency (EPA) health risk assessment model was used to evaluate the health risks of VOCs emitted by the carbon industry. The results showed that the concentration of VOCs in the production areas of the three research enterprises was between 89.77-964.60 µg·m-3, and the management area was between 51.46-121.59 µg·m-3. Naphthalene and carbon disulfide were at the highest concentrations in the carbon plants. The ozone formation potential of VOCs in the production area was between 75.42-1416.73 µg·m-3, and in the management area was between 65.32-202.42 µg·m-3, mainly from the contribution of aromatic hydrocarbons and olefins. The carcinogenic health risk (Risk) of VOCs in the production area was 3.5×10-5-2.8×10-3, and in the management area was 2.0×10-5-9.4×10-5, which was higher than the maximum acceptable level recommended by the EPA (10-6). The non-carcinogenic health risk index (HI) of the VOCs in the production area was 3.2-1.4×102, and in the management area was 4.3×10-1-3.8, except for the management area of the first enterprise, which was greater than 1, which may expose the workers. These health factors cause cancer and non-carcinogenic hazards.
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Poluentes Atmosféricos , Saúde Ambiental , Medição de Risco , Compostos Orgânicos Voláteis , Carbono , Monitoramento Ambiental , HumanosRESUMO
This study investigated whether overexpression of paired-related homeobox 1 (prrx1) can successfully induce differentiation of brown adipose-derived stem cells (BADSCs) into sinus node-like cells. The experiments were performed in two groups: adenovirus-green fluorescent protein (Ad-GFP) group and Ad-prrx1 group. After 5-7 days of adenoviral transfection, the expression levels of sinus node cell-associated pacing protein (hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 [HCN4]) and ion channel (calcium channel, voltage-dependent, T type, alpha 1G subunit [Cacna1g]), as well as transcription factors (T-box 18 [TBX18], insulin gene enhancer binding protein 1 [ISL-1], paired-like homeodomain transcription factor 2 [pitx2], short stature homeobox 2 [shox2]), were detected by western blot and reverse transcription-quantitative polymerase chain reaction. Immunofluorescence assay was carried out to detect whether prrx1 was coexpressed with HCN4, TBX18, and ISL-1. Finally, whole-cell patch-clamp technique was used to record pacing current hyperpolarization-activated inward current (If). The isolated cells were CD90+, CD29+, and CD45-, indicating that pure BADSCs were successfully isolated. After 5-7 days of Ad transfection into cells, the mRNA levels and protein levels of pacing-related factors (TBX18, ISL-1, HCN4, shox2, and Cacna1g) in Ad-prrx1 group were significantly higher than those in Ad-GFP group. However, the expression level of pitx2 was decreased. Immunofluorescence analysis showed that prrx1 was coexpressed with TBX18, ISL-1, and HCN4 in the Ad-prrx1 group, which did not appear in the Ad-GFP group. Whole-cell patch clamps were able to record the If current in the experimental group rather than in the Ad-GFP group. Overexpression of prrx1 can successfully induce sinus node-like cells.
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Tecido Adiposo Marrom/fisiologia , Células-Tronco Adultas/fisiologia , Diferenciação Celular/genética , Proteínas de Homeodomínio/fisiologia , Nó Sinoatrial/fisiologia , Tecido Adiposo Marrom/citologia , Células-Tronco Adultas/citologia , Animais , Transdiferenciação Celular/genética , Células Cultivadas , Masculino , Ratos , Ratos Sprague-Dawley , Nó Sinoatrial/citologia , TransfecçãoRESUMO
BACKGROUND: Long non-coding RNAs (lncRNA) plasmacytoma variant translocation 1 (PVT1) has been shown to be associated with liver fibrosis. Nevertheless, the role of PVT1 in atrial fibrosis remains undefined. This study aims to elucidate the pathophysiological role of lncRNA PVT1 in the regulation of atrial fibrosis and to explore the underlying mechanism. METHODS: Expression of PVT1, miR-128-sp, and Sp1 were examined in human atrial muscle tissues and angiotensin-II (Ang-II)-induced human atrial fibroblasts. Furthermore, the role of PVT1 in regulating atrial fibrosis in Ang-II-treated human atrial fibroblasts and Ang-II-induced atrial fibrosis in mice was investigated. Moreover, the interaction among PVT1, miR-128-3p, and Sp1 were examined using bioinformatics, expression correlation analysis, gain- or loss-of-function assays, RIP assays, and luciferase reporter assays. The involvement of transforming growth factor beta 1 (TGF-ß1)/Smad pathway in this process was also explored. RESULTS: PVT1 was increased in atrial muscle tissues from AF patients and positively with collagen I and collagen III. In vitro assay revealed that PVT1 overexpression facilitated the Ang-II-induced atrial fibroblasts proliferation, collagen production, and TGF-ß1/Smad signaling activation, whereas PVT1 knockdown caused the opposite effect. In vivo assay further confirmed that PVT1 knockdown attenuated the Ang-II-induced mouse atrial fibrosis. Mechanically, PVT1 acted as a sponge for miR-128-3p to facilitate Sp1 expression, thereby activating the TGF-ß1/Smad signaling pathway. CONCLUSION: LncRNA PVT1 promotes atrial fibrosis via miR-128-3p-SP1-TGF-ß1-Smad axis in atrial fibrillation.
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Fibrilação Atrial , Átrios do Coração/patologia , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Proteínas Smad/metabolismo , Fator de Transcrição Sp1/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Adulto , Angiotensina II/farmacologia , Animais , Fibrilação Atrial/metabolismo , Fibrilação Atrial/patologia , Fibrilação Atrial/fisiopatologia , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Colágeno Tipo II/metabolismo , Feminino , Fibroblastos/metabolismo , Fibrose , Átrios do Coração/metabolismo , Átrios do Coração/fisiopatologia , Humanos , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Shensong Yangxin (SSYX), a traditional Chinese herbal medicine, has long been used clinically to treat arrhythmias in China. However, the mechanism of SSYX on atrial fibrillation (AF) is unknown. In this study, we tested the hypothesis that the effect of SSYX on the progression of paroxysmal AF is correlated with the regulation of autonomic nerve activity. METHODS: Eighteen mongrel dogs were randomly divided into control group (n = 6), pacing group (n = 6), and pacing + SSYX group (n = 6). The control group was implanted with pacemakers without pacing; the pacing group was implanted with pacemakers with long-term intermittent atrial pacing; the pacing + SSYX group underwent long-term intermittent atrial pacing and SSYX oral administration. RESULTS: Compared to the pacing group, the parameters of heart rate variability were lower after 8 weeks in the pacing + SSYX group (low-frequency [LF] component: 20.85 ± 3.14 vs. 15.3 ± 1.89 ms 2 , P = 0.004; LF component/high-frequency component: 1.34 ± 0.33 vs. 0.77 ± 0.15, P < 0.001). The atrial effective refractory period (AERP) was shorter and the dispersion of the AERP was higher after 8 weeks in the pacing group, while the changes were suppressed by SSYX intake. The dogs in the pacing group had more episodes and longer durations of AF than that in the pacing + SSYX group. SSYX markedly inhibited the increase in sympathetic nerves and upregulation of tumor necrosis factor-alpha and interleukin-6 expression in the pacing + SSYX group. Furthermore, SSYX suppressed the decrease of acetylcholine and α7 nicotinic acetylcholine receptor protein induced by long-term intermittent atrial pacing. CONCLUSIONS: SSYX substantially prevents atrial electrical remodeling and the progression of AF. These effects of SSYX may have association with regulating the imbalance of autonomic nerve activity and the cholinergic anti-inflammatory pathway.
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Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Acetilcolina/sangue , Animais , Vias Autônomas/efeitos dos fármacos , Western Blotting , Cães , Eletrofisiologia , Ensaio de Imunoadsorção Enzimática , Frequência Cardíaca/efeitos dos fármacos , Imuno-Histoquímica , Interleucina-6/sangue , Modelos Animais , Fator de Necrose Tumoral alfa/sangue , Receptor Nicotínico de Acetilcolina alfa7/sangueRESUMO
BACKGROUND: The purpose of this study was to investigate whether transcatheter renal sympathetic denervation (RSD) interfere with the development of left ventricular (LV) mechanical dyssynchrony during the progression of heart failure (HF). METHODS: Nineteen beagles were randomly divided into sham-operated group (six dogs), control group (seven dogs), and RSD group (six dogs). Sham-operated group were implanted with pacemakers without pacing; Control group were implanted with pacemakers and underwent 3 weeks of rapid right ventricular pacing; and RSD group underwent catheter-based RSD bilaterally and were simultaneously implanted with pacemakers. Both LV strain and LV dyssynchrony were analyzed via 2D speckle-tracking strain echocardiography to evaluate LV function. Longitudinal dyssynchrony was determined as the standard deviation for time-to-peak speckle-tracking strain on apical 4- and 2-chamber views. Radial and circumferential dyssynchrony was determined as the standard deviation for time-to-peak speckle-tracking strain in mid- and base-LV short-axis views. Each myocardial function was also evaluated by averaging the peak systolic strains. LV systolic pressure (LVSP) and LV end-diastolic pressure (LVEDP) were measured. The LV interstitial fibrosis was determined by histological analysis. Plasma angiotensin II (Ang II), aldosterone and norepinephrine (NE) levels were also measured. RESULTS: After 3 weeks, all of the dogs in both the control and RSD groups showed greater LV end-diastolic volume compared with the sham-operated group; however, the dogs in the RSD group had a higher LV ejection fraction (LVEF) than the dogs in the control group (p<0.001). The LV systolic strains were higher in the RSD group than in the control group (p<0.001 for longitudinal, circumferential and radial strain, respectively). The levels of LV dyssynchrony were lower in the RSD group than in the control group (p<0.001 for longitudinal, circumferential and radial dyssynchrony, respectively). Compared with dogs with control alone, RSD dogs had lower LV end-diastolic pressures and less fibrous tissue. The levels of plasma Ang II, aldosterone and NE were lower in the RSD group than in the control group. CONCLUSIONS: RSD inhibites the development of left ventricular mechanical dyssynchrony during the progression of heart failure in dogs.
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Insuficiência Cardíaca/fisiopatologia , Rim/inervação , Rim/cirurgia , Simpatectomia/métodos , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/prevenção & controle , Animais , Progressão da Doença , Cães , Ecocardiografia , Técnicas de Imagem por Elasticidade , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico por imagem , Volume Sistólico , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico por imagemRESUMO
OBJECTIVE: To investigate the effect of temperature on hospital admission among patients with chronic systolic heart failure (CSHF). METHODS: Data regarding in-hospital patients with CSHF were gathered from 12 hospitals in Hubei province, between 2000 and 2010. Patients with a history of congenital heart disease and the history of cancer from this series, were excluded. Chi-square (χ(2)) tests and t tests were used for descriptive analysis. Univariate and multivariate logistic regression methods were performed to determinate the risk of hospital admission of every month to compare with the previous one. We used 2-tailed 95% confidence interval (CI), and tests with P < 0.01 to consider the significant levels, statistically. We also used the SPSS 13.0 for Windows, release 15, 2006 (SPSS Inc, Chicago, Ill) for data analyses. RESULTS: (1) 48 964 patients were enrolled in the present study. The numbers of admission increased 18.71%, 13.84%, -21.90%, -34.62%, -21.97%, -3.81%, -2.04%, 10.13%, -17.13%, -0.85%, 21.54% and 42.70% from January to December when compared to the average number of admission. (2) The odds ratios (ORs) (95% CI, P values) of hospital admission in January, February and December were 1.09 (0.96 - 1.23, 0.54), 0.98 (0.84 - 1.10, 0.46) and 0.96 (0.84 - 1.08, 0.59), respectively in females which did not show any significant differences when compared to the number in August. However the ratios were 0.61 (0.54 - 0.69, < 0.01), 0.80 (0.68 - 0.92, < 0.01) and 0.73 (0.64 - 0.83, < 0.01), respectively, in males that showed significant differences when, compared to the figures in August. (3) The OR of admission increased more when temperature got lower for patients with coronary artery disease, hypertension heart disease or rheumatic heart disease, but not with dilated cardiomyopathy. (4) The OR of admission showed a different impact on patients with different occupation, along with the change of temperature. Low or high temperature did not seem to have different effects on the OR of admission in patients who were free-lanced or unemployed. CONCLUSION: Temperature seemed to have significant effects on the risk of admission, which related to gender, etiology or occupation.
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Insuficiência Cardíaca , Pacientes Internados/estatística & dados numéricos , Temperatura , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Clima , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To evaluate the current status of chronic heart failure (CHF) in Hubei province and analyze the epidemiology of CHF including the general condition, etiology and pharmacological therapy. METHODS: Data of in-hospital patients with CHF were investigated between 2000 and 2010 from 12 hospitals in Hubei Province. INCLUSION CRITERIA: over 18 years of age, organic heart disease and with the symptom of HF including dyspnea and fatigue. Patients with a history of myocardial infarction in the prior 12 months, congenital heart disease, pericardial disease and the history of cancer were excluded. RESULTS: (1) A total of 12 450 patients were enrolled (7166 male, 57.56%). The average age was (62.0 ± 14.5) years. Patients in the scale of age ≥ 80, 70 - 79, 60 - 69, 50 - 59, 40 - 49 and < 40 was 9.53% (1187/12 450), 30.80% (3835/12 450), 23.45% (2920/12 450), 18.81% (2342/12 450), 10.73% (1336/12 450) and 6.67% (830/12 450), respectively (P < 0.01). The NYHA class I, II, III and IV was 0.60%, 23.20%, 50.31% and 26.50%, respectively. (2) The age of patients was significant reduced from 2000 - 2003, 2004 - 2006 to 2007 - 2010 [(66.4 ± 14.1) years, (64.9 ± 14.4) years and (64.2 ± 14.8) years, P < 0.01]. (3) The major causes of CHF were hypertension (31.54%), coronary heart disease (28.24%), dilated cardiomyopathy (26.57%) and rheumatic valvular heart disease (17.49%). The most frequent etiology for CHF was rheumatic valvular heart disease in patients aged less than 40 years old, dilated cardiomyopathy in patients aged 40 - 49 and 50 - 59 years and hypertension in patients aged 60-69, 70-79 and ≥ 80 years. (4) Drug use was as follows: Digitalis (47.49%), diuretics (68.75%), ACEI (50.66%), ß-blocker (44.06%) and aldosterone antagonist (53.08%). Use of digitalis (Wald χ(2) = 903.41, P < 0.01;r = 0.271, P < 0.01), diuretics (Wald χ(2) = 818.05, P < 0.01; r = 0.249, P < 0.01), aldosterone antagonists (Wald χ(2) = 76.92, P < 0.01; r = 0.091, P < 0.01) increased while the ß-blocker (Wald χ(2) = 160.65, P < 0.01; r = -0.117, P < 0.01) declined in proportion to NYHA class increase. CONCLUSIONS: The age of in-hospital patients with CHF declined in the previous 10 years. The primary etiology was hypertension for aged CHF in-hospital patients with CHF. There was big gap between guideline recommended standard therapy and current drug use for in-hospital patients with CHF in Hubei province.