Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 37
Filtrar
1.
Int Heart J ; 62(3): 607-615, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34054001

RESUMO

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/métodos
2.
Mol Biol Rep ; 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34032975

RESUMO

Fluvastatin, a traditional fat-decreasing drug, is widely used for curing cardiovascular disease. Previous reports demonstrated that fluvastatin pretreatment protected against myocardial ischemia/reperfusion (I/R) by inhibiting TLR4 signaling pathway and/or reducing proinflammatory cytokines. However, whether fluvastatin has a cardioprotective effect against apoptosis and autophagy remains unknown. This study aims to evaluate whether the cardioprotective role of fluvastatin in I/R is mediated by high-mobility group box 1 (HMGB1)/toll-like receptor 4 (TLR4) pathway via anti-apoptotic and anti-autophagic functions. Sprague-Dawley rats were anesthetized, artificially ventilated and subjected to 30 min of coronary occlusion, followed by 4 h of reperfusion. The animals were randomized into four groups: (i) Sham operation; (ii) I/R; (iii) I/R + low-dosage fluvastatin (10 mg/kg); and (iv) I/R + high-dosage fluvastatin (20 mg/kg). After reperfusion, the hemodynamic parameters, myocardial infarct size, structural alteration of myocardium, apoptosis index, pro-inflammatory cytokine production, Beclin-1, Light chain 3 (LC3), HMGB1, TLR4 and Nuclear factor kappa B (NF-κB) protein levels were measured and recorded. It was found that fluvastatin preconditioning improved left ventricular dysfunction, reduced HMGB1/TLR4/NF-κB expressions, and inhibited cardiomyocyte apoptosis, autophagy, and inflammation reaction. Moreover, treatment with fluvastatin ameliorated myocardial injury by reducing infarct size, causing less damage to cardiac structure, downregulating autophagy-related protein expression and releasing pro-inflammation mediators. Our findings indicate that fluvastatin exerts beneficial effects on cardiac ischemic damage, which may be associated with its anti-autophagic and anti-apoptotic functions via inhibition of HMGB1/TLR4-related pathway during I/R injury.

4.
Front Plant Sci ; 11: 1216, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32849753

RESUMO

Leaf temperature changes with incident light intensity, but it is unclear how the concurrent changes influence leaf photosynthesis. We examined the time courses of CO2 gas exchanges and chlorophyll fluorescence of seedling leaves in four tropical tree species in response to lightflecks under three different temperature conditions. The three conditions were two constant temperatures at 30°C (T 30) and 40°C (T 40), and a simulated gradually changing temperature from 30 to 40°C (T dyn). The time required to reach 50% of the full photosynthetic induction under T 40 was similar to, or even larger than, that under T 30. However, the induction of assimilation rate (A) and electron transport rate of photosystem II (ETR II) and Rubisco activation process were generally accelerated under T dyn compared to those at either T 30 or T 40. The acceleration in photosynthetic induction under T dyn was significantly greater in the shade-tolerant species than in the shade-intolerant species. A modified photosynthetic limitation analysis indicated that the acceleration was likely to be mainly due to ETR II at the early stage of photosynthetic induction. The study suggests that concurrent increases in leaf temperature with light may increase leaf carbon gain under highly fluctuating light in tropical tree seedlings, particularly in shade-tolerant species.

5.
Front Pharmacol ; 10: 1349, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31803053

RESUMO

Background: Cardiac fibrosis after myocardial infarction mainly causes cardiac diastolic and systolic dysfunction, which results in fatal arrhythmias or even sudden death. Id2, a transcriptional repressor, has been shown to play an important role in the development of fibrosis in various organs, but its effects on cardiac fibrosis remain unclear. This study aimed to explore the effects of Id2 on cardiac fibrosis after myocardial infarction and its possible mechanisms. Methods: This study was performed in four experimental groups: control group, treatment group (including TGF-ß1, hypoxia or MI), treatment+GFP group and treatment+Id2 group. In vitro anoxic and fibrotic models were established by subjecting CFs or NRVMs to a three-gas incubator or TGF-ß1, respectively. An animal myocardial infarction model was established by ligating of the left anterior descending coronary artery followed by directly injecting of Id2 adenovirus into the myocardial infarct's marginal zone. Results: The results showed that Id2 significantly improved cardiac EF and attenuated cardiac hypertrophy. The mRNA and protein levels of α-SMA, Collagen I, Collagen III, MMP2 and TIMP1 were higher in treatment+Id2 group than those in treatment group as well as in treatment+GFP group both in vivo and in vitro. Immunofluorescence revealed that both α-SMA and vimentin were co-expressed in the treatment group and GFP group, but the co-expression were not detected in the control group and Id2 group. Additionally, our findings illustrated that Id2 had protective effects demonstrated by its ability to inhibit the TGF-ß1/Smad3/HIF-1α/IL-11 signaling pathways. Besides, over-expression of Id2 reduced cardiomyocytes apoptosis. Conclusion: In conclusion, this study demonstrated that over-expression of Id2 preserved cardiac function and ameliorated adverse cardiac remodeling, which might be a promising treatment target for cardiac fibrosis and apoptosis.

6.
DNA Cell Biol ; 38(11): 1313-1322, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31545082

RESUMO

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.


Assuntos
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 , Transfecção
7.
Eur J Pharmacol ; 853: 289-298, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30978318

RESUMO

C1q/TNF-related protein-9(CTRP9) is an adipose cytokine, a closest adiponectin paralog, which has anti-inflammatory, antioxidant, vasodilation and anti-atherosclerosis effects. In addition, it can increase insulin sensitivity, decrease blood glucose level and inhibit the apoptosis of endothelial cells. However, it remains unclear whether CTRP9 has beneficial effects on diabetic retinopathy (DR). An adenoviral vector expressing CTRP9 was intravenously injected into db/db mice, aged 12 weeks, at day 15 post injection, and the process was repeated. The transfection efficiency of CTRP9 was assessed by enzyme linked immunosorbent assay. We used RT-PCR, immunofluorescence, and Western blot to determine proinflammatory cytokines, adhesion molecules and tight-junction proteins. The breakdown of blood-retinal barrier (BRB) was evaluated using Evans blue and retinal staining. CTRP9 suppresses the expression of interleukin-1 beta, tumor necrosis factor-alpha, monocyte chemotactic protein-1 and adhesion molecules in the retina of db/db mice. CTRP9 can balance the expression of pigment epithelium-derived factor and vascular endothelial growth factor. CTRP9 can also inhibit the activation of nuclear factor Kappa B in the retina of db/db mouse. In addition, CTRP9 can prevent the breakdown of BRB and downregulation of tight-junction proteins in the retina of db/db mice. Evans blue assay revealed the breakdown of BRB and vascular leakage in the retinas of diabetic mice. CTRP9 can both qualitatively and quantitatively alleviate the vascular leakage in the early stage of diabetic retinas. CTRP9 can inhibit the inflammation of diabetic retinopathy and protect blood-retinal barrier via decreasing proinflammatory cytokines and preventing the downregulation of tight-junction proteins.


Assuntos
Adiponectina/metabolismo , Glicoproteínas/metabolismo , Retina/metabolismo , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Quimiocina CCL2/metabolismo , Inflamação/sangue , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Camundongos , NF-kappa B/metabolismo , Fator de Crescimento Derivado de Plaquetas/metabolismo , Receptores de Adiponectina/genética , Transcrição Genética/efeitos dos fármacos , Molécula 1 de Adesão de Célula Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
8.
Int J Mol Med ; 43(2): 879-889, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30483766

RESUMO

Hybrid approaches combining gene­ and cell­based therapies to make biological pacemakers are a promising therapeutic avenue for bradyarrhythmia. The present study aimed to direct adipose tissue­derived stem cells (ADSCs) to differentiate specifically into cardiac pacemaker cells by overexpressing a single transcription factor, insulin gene enhancer binding protein 1 (ISL­1). In the present study, the ADSCs were transfected with ISL­1 or mCherry fluorescent protein lentiviral vectors and co­cultured with neonatal rat ventricular cardiomyocytes (NRVMs) in vitro for 5­7 days. The feasibility of regulating the differentiation of ADSCs into pacemaker­like cells by overexpressing ISL­1 was evaluated by observation of cell morphology and beating rate, reverse transcription­quantitative polymerase chain reaction analysis, western blotting, immunofluorescence and analysis of electrophysiological activity. In conclusion, these data indicated that the overexpression of ISL­1 in ADSCs may enhance the pacemaker phenotype and automaticity in vitro, features which were significantly increased following co­culture induction.


Assuntos
Tecido Adiposo/citologia , Sistema de Condução Cardíaco/citologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Animais , Biomarcadores , Células Cultivadas , Técnicas de Cocultura , Fenômenos Eletrofisiológicos , Imunofluorescência , Expressão Gênica , Imunofenotipagem , Masculino , Ratos , Transfecção
9.
Ying Yong Sheng Tai Xue Bao ; 29(6): 1829-1838, 2018 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-29974691

RESUMO

Qinghai-Tibetan Plateau, one of the regions on the earth that receives the most solar radiation, is the world's highest alpine meadow ecosystem, with significance to regional and global carbon cycles. To examine the effects of solar radiation on ecosystem carbon dynamics in an alpine meadow, the net ecosystem CO2 exchange (NEE), solar radiation, diffuse radiation, and related environmental variables were measured using eddy-covariance technique and micro-meteorological system. Sky conditions were divided into three categories of clear days (CI≥0.7), cloudy days (0.315 ℃. Under clear sky day conditions, Re increased with increasing CI due to the increases of air temperature, with negative effects on NEE. NEE increased with the increases of VPD up to 0.6 kPa, then slowly decreased when VPD>0.6 kPa, illustrating that NEE was reduced due to the relatively high VPD. Our results suggested that strong solar radiation on clear days would not increase carbon uptake capacity of alpine meadow, while cloudy days with clearness index of 0.6-0.7 would help increase carbon sequestration on the Qinghai-Tibetan Plateau.


Assuntos
Carbono , Ecossistema , Pradaria , Dióxido de Carbono , China , Tibet
10.
Biochem Biophys Res Commun ; 499(2): 143-149, 2018 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-29534968

RESUMO

Regulator of G-protein signalling 5 (RGS5) is, highly expressed in different cell types of the adult human heart, and it is a negative regulator of G protein-mediated signalling that inactivates Gα(q) and Gα(i) and thereby inhibits many signalling pathways. However, the critical role of RGS5 in the pathology of myocardial infarction (MI) remains unexplored. Here, an in vitro MI model, induced by the permanent ligation of the left anterior descending coronary artery, was used with the isolated hearts of wild type (WT) and RGS5-knockout (KO) mice. Our results showed that the loss of RGS5 decreased the post-MI survival rate and left ventricular (LV) function and increased the infarct size. Additionally, the RGS5 knockout mice exhibited greater inflammation, apoptosis, and ventricular remodelling compared with WT-MI mice. Mechanistically, RGS5 loss activated the pathological response mainly by affecting the NF-κB and MAPK signalling pathways. Therefore, our data strongly indicate that RGS5 is a novel modulator of pathological progression after MI that functions NF-κB and MAPK signalling.


Assuntos
Sistema de Sinalização das MAP Quinases , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , NF-kappa B/metabolismo , Proteínas RGS/metabolismo , Remodelação Ventricular , Animais , Morte Celular , Deleção de Genes , Inflamação/complicações , Inflamação/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/enzimologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia
11.
Mol Med Rep ; 17(4): 5074-5080, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29393433

RESUMO

Inflammation serves a critical role in driving sympathetic neural remodeling following myocardial infarction (MI), and activin A has been implicated as an important mediator of the inflammatory response post­MI. However, whether activin A impacts sympathetic neural remodeling post­MI remains unclear. In the present study, the authors assessed the effects of activin A on sympathetic neural remodeling in a rat model of MI. Rats were randomly divided into sham, MI, and MI + follistatin­300 (FS, activin A inhibitor) groups. Cardiac tissues from the peri­infarct zone were assessed for expression of sympathetic neural remodeling and inflammatory factors in rats 4 weeks post­MI by western blotting and immunohistochemical methods. Heart function was assessed by echocardiography. It is demonstrated that FS administration significantly reduced post­MI upregulation of activin A, nerve growth factor protein lever, and the density of nerve fibers with positive and protein expression of sympathetic neural remodeling markers in nerve fibers, which included growth associated protein 43 and tyrosine hydroxylase. In addition, inhibition of activin A reduced cardiac inflammation post­MI based on the reduction of i) interleukin­1 and tumor necrosis factor­α protein expression, ii) numbers and/or proportional area of infiltrating macrophages and myofibroblasts and iii) phosphorylated levels of p65 and IκBα. Furthermore, activin A inhibition lessened heart dysfunction post­MI. These results suggested that activin A inhibition reduced sympathetic neural remodeling post­MI in part through inhibition of the inflammatory response. The current study implicates activin A as a potential therapeutic target to circumvent sympathetic neural remodeling post-MI.


Assuntos
Ativinas/metabolismo , Sistema Nervoso Simpático , Remodelação Ventricular , Animais , Biomarcadores , Citocinas/metabolismo , Modelos Animais de Doenças , Folistatina/farmacologia , Testes de Função Cardíaca , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia , NF-kappa B/metabolismo , Ratos , Sistema Nervoso Simpático/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos
12.
Chin Med J (Engl) ; 130(14): 1639-1647, 2017 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-28685712

RESUMO

BACKGROUND: Pharmacological therapy for congestive heart failure (CHF) with ventricular arrhythmia is limited. In the study, our aim was to evaluate the effects of Chinese traditional medicine Shensong Yangxin capsules (SSYX) on heart rhythm and function in CHF patients with frequent ventricular premature complexes (VPCs). METHODS: This double-blind, placebo-controlled, multicenter study randomized 465 CHF patients with frequent VPCs to the SSYX (n = 232) and placebo groups (n = 233) for 12 weeks of treatment. The primary endpoint was the VPCs monitored by a 24-h ambulatory electrocardiogram. The secondary endpoints included the left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter, N-terminal pro-brain natriuretic peptide (NT-proBNP), New York Heart Association (NYHA) classification, 6-min walking distance (6MWD), Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores, and composite cardiac events (CCEs). RESULTS: The clinical characteristics were similar at baseline. SSYX caused a significantly greater decline in the total number of VPCs than the placebo did (-2145 ± 2848 vs. -841 ± 3411, P < 0.05). The secondary endpoints of the LVEF, NYHA classification, NT-proBNP, 6MWD, and MLHFQ scores showed a greater improvements in the SSYX group than in the placebo group (ΔLVEF at 12th week: 4.75 ± 7.13 vs. 3.30 ± 6.53; NYHA improvement rate at the 8th and 12th week: 32.6% vs. 21.8%, 40.5% vs. 25.7%; mean level of NT-proBNP in patients with NT-proBNP ≥125 pg/ml at 12th week: -122 [Q1, Q3: -524, 0] vs. -75 [Q1, Q3: -245, 0]; Δ6MWD at 12th week: 35.1 ± 38.6 vs. 17.2 ± 45.6; ΔMLHFQ at the 4th, 8th, and 12th week: -4.24 ± 6.15 vs. -2.31 ± 6.96, -8.19 ± 8.41 vs. -3.25 ± 9.40, -10.60 ± 9.41 vs. -4.83 ± 11.23, all P < 0.05). CCEs were not different between the groups during the study period. CONCLUSIONS: In this 12-week pilot study, SSYX was demonstrated to have the benefits of VPCs suppression and cardiac function improvement with good compliance on a background of standard treatment for CHF. TRIAL REGISTRATION: www.chictr.org.cn, ChiCTR-TRC-12002061 (http://www.chictr.org.cn/showproj.aspx?proj=7487) and Clinicaltrials.gov, NCT01612260 (https://clinicaltrials.gov/ct2/show/NCT01612260).


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , Complexos Ventriculares Prematuros/tratamento farmacológico , Adolescente , Adulto , Idoso , Método Duplo-Cego , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Insuficiência Cardíaca/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Função Ventricular Esquerda/efeitos dos fármacos , Complexos Ventriculares Prematuros/metabolismo , Adulto Jovem
13.
Chin Med J (Engl) ; 130(2): 171-178, 2017 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-28091409

RESUMO

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.


Assuntos
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/sangue
14.
Int J Mol Med ; 38(5): 1403-1410, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27632938

RESUMO

T-box 18 (TBX18) plays a crucial role in the formation and development of the head of the sinoatrial node. The objective of this study was to induce adipose-derived stem cells (ADSCs) to produce pacemaker-like cells by transfection with the TBX18 gene. A recombinant adenovirus vector carrying the human TBX18 gene was constructed to transfect ADSCs. The ADSCs transfected with TBX18 were considered the TBX18-ADSCs. The control group was the GFP-ADSCs. The transfected cells were co-cultured with neonatal rat ventricular cardiomyocytes (NRVMs). The results showed that the mRNA expression of TBX18 in TBX18-ADSCs was significantly higher than in the control group after 48 h and 7 days. After 7 days of co-culturing with NRVMs, there was no significant difference in the expression of the myocardial marker cardiac troponin I (cTnI) between the two groups. RT-qPCR and western blot analysis showed that the expression of HCN4 was higher in the TBX18-ADSCs than in the GFP-ADSCs. The If current was detected using the whole cell patch clamp technique and was blocked by the specific blocker CsCl. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSCMs) showed approximately twice the current density compared with the ADSCs. Our study indicated that the TBX18 gene induces ADSCs to differentiate into pacemaker­like cells in the cardiac microenvironment. Although further experiments are required in order to assess safety and efficacy prior to implementation in clinical practice, this technique may provide new avenues for the clinical therapy of bradycardia.


Assuntos
Diferenciação Celular , Microambiente Celular , Células-Tronco/metabolismo , Proteínas com Domínio T/genética , Tecido Adiposo/citologia , Animais , Animais Recém-Nascidos , Western Blotting , Células Cultivadas , Técnicas de Cocultura , Expressão Gênica , Humanos , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Masculino , Potenciais da Membrana , Miocárdio/citologia , Miocárdio/metabolismo , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/fisiologia , Técnicas de Patch-Clamp , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células-Tronco/citologia , Células-Tronco/fisiologia , Proteínas com Domínio T/metabolismo , Troponina I/genética , Troponina I/metabolismo
15.
Eur J Pharmacol ; 789: 319-327, 2016 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-27477354

RESUMO

Activin A is a key regulator of cardiac fibrosis. However, little is known about the mechanisms by which it contributes to cardiac fibrosis. Our study explored the effects of activin A on proliferation and differentiation of adult rat cardiac fibroblasts (CFs) via the activin A receptor, activin receptor-like kinase 4 (ALK4). CF proliferation was measured by CCK8 and EdU assays, while differentiation, fibrosis and signaling were measured by western blot analysis of α-smooth muscle actin, collagen type I, phosphorylated extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (p38-MAPK) expression. Activin A levels were measured by ELISA and western blot analysis. We demonstrated that CFs express activin A and its expression was significantly enhanced by angiotensin II (Ang II), but follistatin (activin A inhibitor) significantly reversed Ang II-induced activin A upregulation, CF proliferation, differentiation, collagen type I expression as well as ERK1/2 and p38-MAPK pathways activation. Conversely, recombinant activin A largely increased these parameters in both the presence and absence of Ang II. Interestingly, p38-MAPK (SB203580) and ALK4 (SB431542) inhibitors significantly reduced all activin A-mediated responses; however, an ERK1/2 inhibitor (PD98059) could only significantly reduce CF proliferation and collagen type I expression but not differentiation. Importantly, the most significant effects were observed in the presence vs. absence of Ang II. Thus, activin A promotes basal and Ang II-induced CF proliferation and differentiation via ALK4, and the effects are partly mediated through the ERK1/2 and p38-MAPK pathways. These data suggest that activin A is a potential therapeutic target for cardiac fibrosis.


Assuntos
Ativinas/farmacologia , Diferenciação Celular/efeitos dos fármacos , Fibroblastos/citologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Receptores de Ativinas Tipo I/metabolismo , Angiotensina II/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Fibroblastos/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Miocárdio/citologia , Ratos , Ratos Sprague-Dawley
16.
Regul Pept ; 192-193: 1-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25058156

RESUMO

Ghrelin is a novel growth hormone-releasing peptide, which has been shown to exert beneficial effects on cardiac function and ventricular remodeling. The present study aimed to investigate the expression of ghrelin and the growth hormone (GH) secretagogue receptor 1a (GHSR-1a), and the association with cardiac remodeling in rats with myocardial infarction (MI). Twenty-four hours after ligation of the anterior descending artery (LAD), adult male Sprague-Dawley rats were randomized to 3 d, 7 d and 28 d group. Sham animals underwent thoracotomy and pericardiotomy, but not LAD ligation. Expression of both ghrelin and GHSR-1a was assessed by means of immunohistochemistry and real-time PCR. Plasma ghrelin levels were measured by ELISA kit. In addition, cardiac remodeling was assessed by echocardiographic and hemodynamic measurements. Plasma and cardiac expression of ghrelin decreased on days 3, 7 and 28 compared with the sham group (P<0.05). In contrast the GHSR-1a mRNA levels increased during the same days (P<0.05). Decreased positive immunoreaction for ghrelin and increased positive GHSR-1a were also observed in the infarcted heart. Interestingly, plasma ghrelin correlated negatively with left ventricular end-diastolic pressure (r=-0.59, P=0.002) and left ventricular end-diastolic dimension (r=-0.73, P<0.01). The ghrelin system may play an important role regulating cardiac remodeling after MI and present as a potential significant target for pharmacological modulation and treating cardiac remodeling.


Assuntos
Vasos Coronários/metabolismo , Vasos Coronários/cirurgia , Grelina/biossíntese , Grelina/genética , Receptores de Grelina/biossíntese , Receptores de Grelina/genética , Animais , Grelina/sangue , Imuno-Histoquímica , Ligadura , Masculino , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real
17.
Chin Med J (Engl) ; 125(14): 2466-71, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22882923

RESUMO

BACKGROUND: Anxiety appears to be more common in patients with coronary artery disease (CHD) than in the general population, and anxiety symptoms may precede onset of CHD and play an important role in development of CHD. Little is known about the prevalence of anxiety symptoms in Chinese patients with premature ventricular contractions (PVCs). Our objective was to study anxiety symptoms and potential risk factors in a Chinese population with PVCs but without structural heart disease. METHODS: The Zung self-rating anxiety scale (ZSAS) was used to assess anxiety symptoms. Correlation between anxiety symptoms and socio-demographics and medical factors were analyzed by Logistic regression. RESULTS: Of 1144 patients with PVCs (487 males and 657 females), age (53 ± 23) years old, disease duration 1 month to 24 years, a total of 381 (33.3%) patients were categorized as having anxiety symptoms. Anxiety symptoms increased with age, low income, low education level, nationality, PVC count/24 hours, bad social support, village settlement type (P < 0.05). Multivariate Logistic regression indicated that six variables-education level, ethnic minorities, dwelling place, age, PVC count/24 hours, and social support-significantly and independently related with anxiety symptoms (P < 0.05). CONCLUSIONS: In the Chinese population, anxiety symptoms in subjects with PVCs were frequent. Education level, ethnic minorities, dwelling place, age, PVC count/24 hours, and social support were independent risk factors for anxiety symptoms. Further research on the relationship between PVCs and anxiety symptoms in China is necessary.


Assuntos
Ansiedade/epidemiologia , Cardiopatias/psicologia , Complexos Ventriculares Prematuros/psicologia , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Peptides ; 32(11): 2357-61, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22008733

RESUMO

Ghrelin is a novel growth hormone-releasing peptide, which has been shown to exert beneficial effects on ventricular remodeling. In this study, we investigated whether ghrelin could decrease vulnerability to ventricular arrhythmias in rats with myocardial infarction and the possible mechanism. Twenty-four hours after ligation of the anterior descending artery, adult male Sprague-Dawley rats were randomized to ghrelin (100 µg/kg) and saline (control group) for 4 weeks. Sham animals underwent thoracotomy and pericardiotomy, but not LAD ligation. Myocardial endothelin-1 (ET-1) levels were significantly elevated in saline-treated rats at the border zone compared with sham-operated rats. Myocardial connexin43 (Cx43) expression at the border zone was significantly decreased in saline-treated infarcted rats compared with sham-operated rats. Ghrelin significantly decreased the inducibility of ventricular tachyarrhythmias compared with control group. Arrhythmias sores during programmed stimulation in saline-treated rats were significantly higher than scores in those treated with ghrelin. The electrophysiological improvement of fatal ventricular tachyarrhythmias was accompanied with increased immunofluorescence-stained Cx43, myocardial Cx43 protein and mRNA levels in ghrelin treated rats. We also shown that ghrelin significantly decreased tissue ET-1 levels at the infarcted border zone. Thus, ghrelin showed the protective effect on ventricular arrhythmias after myocardial infarction. Although the precise mechanism by which ghrelin modulates the dephosphorylation of Cx43 remains unknown, it is most likely that the ghrelin increased expression of Cx43 through the inhibition of ET-1.


Assuntos
Arritmias Cardíacas/metabolismo , Conexina 43/metabolismo , Vasos Coronários/metabolismo , Endotelina-1/metabolismo , Grelina/administração & dosagem , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Potenciais de Ação , Animais , Arritmias Cardíacas/complicações , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/fisiopatologia , Conexina 43/genética , Vasos Coronários/patologia , Modelos Animais de Doenças , Eletrocardiografia , Endotelina-1/genética , Expressão Gênica , Grelina/metabolismo , Grelina/uso terapêutico , Ligadura , Masculino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/fisiopatologia , Miocárdio/patologia , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Remodelação Ventricular/efeitos dos fármacos
19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 19(2): 485-90, 2011 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-21518514

RESUMO

This study was purposed to construct a fusion DNA vaccine containing WT1 multi-epitope and stimulating epitope of mycobacterium tuberculosis heat shock protein 70 and to detect its expression and immunogenicity. On the basis of published data, a multi-epitope gene (Multi-WT1) containing three HLA *0201-restricted CTL epitopes: one HLA*2402-restricted CTL epitope, two Th epitopes and one universal Th Pan-DR epitope (PADRE) was constructed. DNA-coding sequence was modified by Computer-Aided Design (CAD) to optimize proteasome-mediated epitope processing through the introduction of different amino acid spacer sequences. The synthetic nucleotide sequence was then inserted into an eukaryotic vector to construct the plasmid pcDNA3.1-WT1.For enhancing CTL activity, HSP70 fragment including stimulatory domain P407-426 was amplified by PCR from mycobacterial HSP70 gene and cloned into pcDNA3.1(+). Then Multi-WT1 was fused to the N-terminal of pcDNA3.1-mHSP70(407-426) to make the multi-epitope fusion gene vaccine pcDNA3.1-WT1-mHSP70(407-426). HEK-293T cells were transfected with this vaccine and the expressed product was identified by RT-PCR. Enzyme-linked immunospot assay (ELISPOT) was used to evaluate the immunological responses elicited by vaccine. The results showed that the most of WT1 epitopes could be correctly cleaved which was confirmed by software Net Chop 3.1 and PAPROCIanalysis. RT-PCR showed correct expression of target gene in HEK293T cells and ELISPOT showed specific T-cell responses. It is concluded that the eukaryotic expression vector PcDNA3.1-WT1-mHSP70(407-426) fusion gene has been successfully constructed and the immunity response is also elicited, which is a good candidate for further research of DNA vaccine.


Assuntos
Proteínas de Bactérias/imunologia , Proteínas de Choque Térmico HSP70/imunologia , Vacinas de DNA/genética , Vacinas de DNA/imunologia , Proteínas WT1/imunologia , Proteínas de Bactérias/genética , Epitopos/genética , Epitopos/imunologia , Vetores Genéticos , Proteínas de Choque Térmico HSP70/genética , Humanos , Epitopos Imunodominantes , Proteínas WT1/genética
20.
Mol Cell Biochem ; 352(1-2): 239-46, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21373807

RESUMO

L-type calcium current (I(Ca)) plays a critical role in excitation-contraction coupling (ECC). Unlike transient outward K(+) current (I(to)), it is controversial whether I(Ca) transmural gradient exists in left ventricle. Although previous studies have shown some evidences for I(Ca) heterogeneity, the mechanism is still unknown. In this study, the authors recorded I(Ca) from epicardial (EPI) and endocardial (ENDO) myocytes isolated from murine left ventricle using patch-clamp technique. It was found that I(Ca) density was obviously larger in EPI than in ENDO (7.3 ± 0.3 pA/pF vs. 6.2 ± 0.2 pA/pF, at test potential of +10 mV, P < 0.05). The characteristics of I(Ca) showed no difference between these two regions except for the fast inactivation time constants (9.9 ± 0.9 ms in EPI vs. 13.5 ± 0.9 ms in ENDO, at test potential of +10 mV, P < 0.05). In addition, it was explored the molecular mechanism underlying I(Ca) transmural gradient by Western blot. The authors demonstrated that a higher activity of CaMKII in ENDO cells induced more nuclear translocation of p65, a component of nuclear factor-kappa B (NF-kB). Consequently, p65 in ENDO inhibited more transcription of Cav1.2, the main encoding gene for L-type calcium channels (LTCCs). These results reveal a difference in CaMKII/p65 signal pathway between EPI and ENDO that underlies this mechanism of I(Ca) heterogeneity in murine left ventricle.


Assuntos
Canais de Cálcio Tipo L/metabolismo , Ventrículos do Coração/metabolismo , Animais , Western Blotting , Camundongos , Técnicas de Patch-Clamp
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...