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1.
J Cell Mol Med ; 22(9): 4344-4353, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29971943

RESUMO

Atrial myocyte hypertrophy is one of the most important substrates in the development of atrial fibrillation (AF). The TWEAK/Fn14 axis is a positive regulator of cardiac hypertrophy in cardiomyopathy. This study therefore investigated the effects of Fn14 on atrial hypertrophy and underlying cellular mechanisms using HL-1 atrial myocytes. In patients with AF, Fn14 protein levels were higher in atrial myocytes from atrial appendages, and expression of TWEAK was increased in peripheral blood mononuclear cells, while TWEAK serum levels were decreased. In vitro, Fn14 expression was up-regulated in response to TWEAK treatment in HL-1 atrial myocytes. TWEAK increased the expression of ANP and Troponin T, and Fn14 knockdown counteracted the effect. Inhibition of JAK2, STAT3 by specific siRNA attenuated TWEAK-induced HL-1 atrial myocytes hypertrophy. In conclusion, TWEAK/Fn14 axis mediates HL-1 atrial myocytes hypertrophy partly through activation of the JAK2/STAT3 pathway.

2.
Biomed Rep ; 6(5): 549-554, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28529736

RESUMO

The purpose of the present study was to compare the efficacy and safety of dabigatran and interrupted warfarin with low-molecular-weight heparin bridging in non-valvular atrial fibrillation (AF) catheter ablation. Previously, there has been concerns that bridging therapy increases bleeding events without the benefit of stroke prevention. It has been suggested that bridging therapy should be considered only for patients at high-risk of thrombosis. Nevertheless, bridging therapy in AF patients with a low CHADS2 score may be safe and effective. The authors performed a prospective, observational study that included consecutive 240 patients undergoing AF ablation in P.R. China. A total of 139 patients received 110 mg dabigatran twice daily and 101 patients took dose-adjusted warfarin that had been bridged with low-molecular-weight heparin. The mean patient age was 55.48 years with 72.1% being men and 74.2% having paroxysmal AF. One thromboembolic complication occurred in the dabigatran group compared to none in the warfarin group. Both the groups presented a similar major bleeding rate, total bleeding rate, and bleeding and thromboembolic complications. In patients undergoing AF ablation, the risk of bleeding or thromboembolic complications was similar for both dabigatran and interrupted warfarin with bridging therapy. Bridging therapy appeared to be safe and effective for the low-risk population.

3.
Nitric Oxide ; 65: 37-42, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28216239

RESUMO

Much effort has been dedicated to exploring the mechanisms of IPC, and the GJ is one of the proposed targets of IPC. Several lines of evidence have indicated that NO affects GJ permeability regulation and expression of connexin isoforms. NO-induced stimulation of the sGC-cGMP pathway and the subsequent PKG activation could lead directly to connexin phosphorylation and GJ coupling modification. Additionally, because NO-induced cardioprotection against I/R injury beyond the cGMP/PKG-dependent pathway has been reported in isolated cardiomyocytes, it has been posited that NO-mediated GJ coupling might be independent from the activation of the NO-induced cGMP/PKG pathway during IPC. S-nitrosylation by NO exerts a major influence in IPC-induced cardioprotection. It has been suggested that NO-mediated cardioprotection during IPC was not dependent on sGC/cGMP/PKG but on SNO signaling. We need more researches to prove that which signaling pathway (S-nitrosylation or protein kinase G activation) is the major one modulating GJ coupling during IPC. The aim of review article is to discuss the possible signaling pathways of NO in regulating GJ during IPC.


Assuntos
Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Junções Comunicantes/fisiologia , Precondicionamento Isquêmico Miocárdico , Óxido Nítrico/metabolismo , Ativação Enzimática , Humanos , Miocárdio/metabolismo , Nitrosação , Transdução de Sinais
4.
Oncotarget ; 7(43): 69243-69255, 2016 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-27655723

RESUMO

Ischemic preconditioning (IPC) maintains connexin43 (Cx43) phosphorylation and reduces chemical gap junction (GJ) coupling in cardiomyocytes to protect against ischemic damage. However, the signal transduction pathways underlying these effects are not fully understood. Here, we investigated whether nitric oxide (NO) and protein kinase C-ε (PKC-ε) contribute to IPC-induced cardioprotection by maintaining Cx43 phosphorylation and inhibiting chemical GJ coupling. IPC reduced ischemia-induced myocardial infarction and increased cardiomyocyte survival; phosphorylated Cx43, eNOS, and PKC-ε levels; and chemical GJ uncoupling. Administration of the NO donor SNAP mimicked the effects of IPC both in vivo and in vitro, maintaining Cx43 phosphorylation, promoting chemical GJ uncoupling, and reducing myocardial infarction. Preincubation with the NO synthase inhibitor L-NAME or PKC-ε translocation inhibitory peptide (PKC-ε-TIP) abolished these effects of IPC. Additionally, by inducing NO production, IPC induced translocation of PKC-ε, but not PKC-δ, from the cytosolic to the membrane fraction in primary cardiac myocytes. IPC-induced cardioprotection thus involves increased NO production, PKC-ε translocation, Cx43 phosphorylation, and chemical GJ uncoupling.


Assuntos
Conexina 43/metabolismo , Junções Comunicantes/metabolismo , Precondicionamento Isquêmico Miocárdico , Óxido Nítrico/metabolismo , Proteína Quinase C-épsilon/metabolismo , Animais , Animais Recém-Nascidos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Inibidores Enzimáticos/farmacologia , Junções Comunicantes/efeitos dos fármacos , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/prevenção & controle , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Doadores de Óxido Nítrico/farmacologia , Fosforilação/efeitos dos fármacos , Ratos Wistar , S-Nitroso-N-Acetilpenicilamina/farmacologia
5.
Med Sci Monit ; 22: 1250-7, 2016 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-27078001

RESUMO

BACKGROUND Plumbagin is a potent antioxidant with anti-inflammatory and anti-carcinogenic action. Myocardial ischemia/reperfusion injury results in organ damage through oxidative stress and inflammatory mechanisms. In this study, we analyzed the potential role of plumbagin against myocardial I/R injury in Wistar rats. MATERIAL AND METHODS Oxidative stress was measured through ROS, lipid peroxide content, and antioxidant enzyme activities. The expression of redox signaling and inflammatory proteins was analyzed through Western blotting. Inflammatory cytokine expressions were determined through ELISA. RESULTS Oxidative stress status was reduced by plumbagin by decreasing ROS and lipid peroxide levels in rats with myocardial I/R (MI/R) injury. Plumbagin regulated redox imbalance induced by I/R injury by modulating the transcription factors NF-κB and Nrf-2. Further, downstream targets of NF-κB (COX-2, iNOS) and Nrf-2 (HO-1, NQO1 and GST) expression were significantly downregulated by plumbagin treatment. Pro-inflammatory cytokine expressions were significantly abrogated by plumbagin treatment. CONCLUSIONS This study shows the protective role of plumbagin against myocardial I/R injury by regulating antioxidant and inflammatory mechanisms.


Assuntos
Traumatismo por Reperfusão Miocárdica/prevenção & controle , Fator 2 Relacionado a NF-E2/metabolismo , Naftoquinonas/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Anticarcinógenos/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos
6.
Asian Pac J Trop Med ; 9(3): 269-73, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26972400

RESUMO

OBJECTIVE: To study the effect of levocarnitine (L-CN) on tissue inhibitor of metalloproteinase-1 (TIMP-1) and intercellular adhesion molecule-1 (ICAM-1) expression of rats with coronary heart disease and evaluate the protective effect of L-CN on myocardial cells. METHODS: High-fat diet feeding and intraperitoneal injection of pituitrin was performed on rats in model group and CHD Model of rats was built. Rats with successful model-building were selected and divided into L-CN group and Ctrl group randomly. Rats in L-CN group were given L-CN treatment, with intraperitoneal injection of 200 mg·kg(-1)·d(-1) and successive administration for 3 d. Rats in Ctrl group were given equal volumes of normal saline. Blood was collected from carotid artery at different time and expression quantity of creatine kinase-MB (CK-MB) and Troponin Ⅰ (TnⅠ) in serum was detected. Rats in each group were put to death and were separated to obtain the myocardial tissue. Real-time PCR and Western Blotting hybridization were performed to detect the TIMP-1, ICAM-1 expression in myocardial tissue in each group. Statistical analysis was employed to explore the expression changes of TIMP-1 and ICAM-1, and ELISA test was used to analyze the expression changes of myocardial necrosis marker-CK-MB and TnⅠto learn the effect of L-CN and its myocardial protective effect. RESULTS: The total cholesterol, triglyceride and blood glucose levels of rats in model group were significantly higher than that in control group, which indicated that due to high-fat diet feeding, blood lipid of rats in model group was obviously higher than that in control group. In myocardial tissue of rats in model group, TIMP-1 level significantly reduced and ICAM-1 level significantly increased (P < 0.01). In model group, after L-CN treatment, TIMP-1 level had double increase, while ICAM-1 level had 43% of decrease in L-CN group compared with Ctrl group. After L-CN intervention treatment, CK-MB and TnⅠ content in L-CN group relatively reduced compared with Ctrl group. The difference among groups was obvious (P < 0.01). CONCLUSIONS: L-CN could increase the TIMP-1 expression level and inhibit the ICAM-1 expression level. L-CN has a certain myocardial protective effect.

7.
Intern Med ; 55(2): 153-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26781015

RESUMO

Acute myocardial infarction, hyperhomocysteinemia and pulmonary tuberculosis (PTB) are rare in individuals under the age of 30 years. We herein report the case of a 27-year-old man who presented with intermittent chest pain, elevated homosysteine level, and PTB. The patient was treated successfully with a combination of medications and percutaneous coronary intervention. This uncommon case highlights that homocysteine, folate and B vitamins levels should be regularly evaluated, and that chest X-rays or thoracic computed tomography should be ordered routinely to exclude PTB in patients under the age of 30 years who present acute myocardial infarction and lack the traditional risk factors.


Assuntos
Hiper-Homocisteinemia/complicações , Infarto do Miocárdio/complicações , Tuberculose Pulmonar/complicações , Doença Aguda , Adulto , Dor no Peito/tratamento farmacológico , Ácido Fólico/sangue , Homocisteína/sangue , Humanos , Hiper-Homocisteinemia/sangue , Masculino , Infarto do Miocárdio/sangue , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Fatores de Risco , Complexo Vitamínico B/sangue
9.
Int J Environ Res Public Health ; 12(9): 11549-59, 2015 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-26389929

RESUMO

In this study, a multiple linear regression model to evaluate the risk of morbidity and mortality of ischemic cardiovascular disease is demonstrated. In this model, predictor variables are selected from physiological chemicals in a blood test of the subjects. Meanwhile, the calculated risk score is selected as a response variable. Four major latent variables including hepatic, nephric, metabolic, and BMI (Body Mass Index) are revealed by performing statistical and principal component analysis for the collected survey data. The analyzed result also shows that the cardiac disorder is correlated with symptoms of abnormal BMI, hepatic disorder, nephric disorder, and metabolic disorder. Thus, the risk of morbidity and mortality of ischemic cardiovascular disease can be assessed from the proposed multiple regression model.


Assuntos
Biomarcadores/sangue , Análise Química do Sangue , Doenças Cardiovasculares/mortalidade , Adulto , Índice de Massa Corporal , Feminino , Humanos , Nefropatias/sangue , Modelos Lineares , Hepatopatias/sangue , Masculino , Doenças Metabólicas/sangue , Pessoa de Meia-Idade , Morbidade , Fatores de Risco
10.
Mol Med Rep ; 12(4): 5746-52, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26252617

RESUMO

The present study investigated the effects of rotigaptide (ZP123) on the expression, distribution and phosphorylation of connexin43 (Cx43) in myocardial cell membranes in cardioversion of ventricular fibrillation (VF). A model of prolonged VF (8, 12 and 30 min) was established in mongrel dogs (n=8/group), following treatment with ZP123 or normal saline (NS control). A sham control was included. Cardiopulmonary resuscitation was begun at the start of VF followed by defibrillation. Animals received a maximum of three defibrillations of increasing energy (70, 100 and 150 J biphasic shock) as required. The average defibrillation energy, defibrillation success rate, return of spontaneous circulation and survival rate were recorded. Cx43 and phosphorylated (p-)Cx43 expression in cardiomyocyte membranes was detected by western blot and immunofluorescence analyses. Compared with the NS-treated control groups, the success defibrillation rate in the 8-min and 12-min ZP123 groups was significantly higher (P<0.05), while the average defibrillation energy was significantly lower (P<0.05). Cx43 expression in the VF groups was significantly lower than that in the sham control group (P<0.05). Cx43 expression was higher in the 12-min and 30-min ZP123 groups than that in the NS control group (P<0.05), while p-Cx43 expression decreased, although the levels were significantly higher than those in the control groups (P<0.05). Cx43 expression was positively correlated with the defibrillation success rate (r=0.91; P<0.01) and negatively with the mean defibrillation energy (r=-0.854; P<0.01), while p-Cx43 expression was positively correlated with the success rate of the previous three defibrillations (r=0.926; P<0.01).In conclusion, ZP123 reduced Cx43 remodeling through regulating the expression, distribution and phosphorylation of Cx43, thereby reducing the defibrillation energy required for successful cardioversion.


Assuntos
Antiarrítmicos/farmacologia , Conexina 43/genética , Cardioversão Elétrica , Regulação da Expressão Gênica/efeitos dos fármacos , Oligopeptídeos/farmacologia , Fibrilação Ventricular/tratamento farmacológico , Animais , Reanimação Cardiopulmonar , Conexina 43/metabolismo , Diástole , Cães , Eletrocardiografia , Feminino , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fosforilação , Sístole , Fibrilação Ventricular/genética , Fibrilação Ventricular/metabolismo , Fibrilação Ventricular/fisiopatologia
11.
Genet Test Mol Biomarkers ; 19(10): 556-60, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26263432

RESUMO

BACKGROUND: Rupture of vulnerable plaque with subsequent thrombus formation has been implicated as the most common pathogenic mechanism responsible for acute coronary syndrome (ACS). Angiographic coronary lesion complexity has been reported to reflect plaque vulnerability. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine and might be involved in the pathophysiology of atherosclerotic plaque destabilization. OBJECTIVE: This study was designed to investigate if serum MIF levels are associated with angiographic coronary lesion complexity in patients with coronary artery disease (CAD). MATERIALS AND METHODS: A total of 232 consecutive CAD patients and 76 controls were recruited. CAD patients were subdivided according to the presence of ACS (n=138) or stable angina pectoris (SAP) (n=98). Coronary lesion morphology was assessed by coronary angiography. Serum MIF levels were measured by an enzyme-linked immunosorbent assay. RESULTS: SAP patients had significantly higher serum MIF levels compared with healthy controls, and ACS patients had significantly higher serum MIF levels compared with SAP patients. In SAP patients, serum MIF levels were independently associated with the presence of complex coronary lesion. In ACS patients, serum MIF levels increased in conjunction with the extent of complex lesions. CONCLUSIONS: Serum MIF levels are a potential biomarker for reflecting the presence and severity of angiographically complex coronary lesion in CAD patients.


Assuntos
Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/patologia , Oxirredutases Intramoleculares/sangue , Fatores Inibidores da Migração de Macrófagos/sangue , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/patologia , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Placa Aterosclerótica/diagnóstico , Placa Aterosclerótica/patologia , Estudos Prospectivos , Fatores de Risco
13.
Mol Cell Biochem ; 400(1-2): 213-22, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25421413

RESUMO

Group I metabotropic glutamate receptors, mGluR1 and mGluR5, are associated with sympathetic nerve activity. Sympathetic nerve stimulation exerts a crucial effect on modulating phosphorylation status and distribution of connexin43 (Cx43) in rat heart. Hence, mGluR1 and mGluR5 have an indirect effect on regulating the function of gap junction channels, which is affected by the availability of Cx43 protein. Additionally, it has been demonstrated that mGluR1/5 are present in ventricular myocardium in particular intercalated disks where Cx43 is the principal component of ventricular gap junction channels. We, therefore, hypothesized that mGluR1/5 might regulate Cx43 phosphorylation and gap junctional intercellular communication (GJIC) directly, independent of sympathetic nerve stimulation. After documenting the presence of mGluR1 and mGluR5 in H9c2 cardiomyoblast cells, addition of the selective mGluR1/5 agonist (S)-3,5-dihydroxyphenylglycine hydrate (DHPG) induced Cx43 phosphorylation and GJIC inhibition in both concentration- and time-dependent manner. The effects of DHPG were abolished by the mGluR1 antagonist LY367385 and the specific inhibitor of MEK1, PD98059 which also reduced phosphorylation of extracellular-signal-regulated protein kinase 1/2 (ERK1/2); but not by the mGluR5 antagonist 6-methyl-2-(phenylethynyl) pyridine hydrochloride or the selective inhibitor of protein kinase C (PKC). In conclusion, in H9c2 cardiomyoblast cells mGluR1 increases Cx43 phosphorylation level and suppresses GJIC involving ERK1/2 but not PKC.


Assuntos
Conexina 43/metabolismo , Receptor de Glutamato Metabotrópico 5/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Animais , Benzoatos/administração & dosagem , Comunicação Celular/genética , Junções Comunicantes/metabolismo , Junções Comunicantes/patologia , Glicina/administração & dosagem , Glicina/análogos & derivados , Glicina/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , MAP Quinase Quinase 1/metabolismo , Metoxi-Hidroxifenilglicol/administração & dosagem , Metoxi-Hidroxifenilglicol/análogos & derivados , Mioblastos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Fosforilação , Ratos , Receptor de Glutamato Metabotrópico 5/genética , Receptores de Glutamato Metabotrópico/genética , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/metabolismo
14.
Ren Fail ; 37(1): 73-6, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25260057

RESUMO

OBJECTIVES: To investigate the association between serum uric acid and mortality in a Chinese population of hypertensive patients. METHODS AND RESULTS: A total of 2757 Chinese hypertensive patients from department of cardiology of several hospitals in Shanghai in China were followed up for about six years in this prospective study. Mortality was recorded and related factors were evaluated. Hyperuricemia was diagnosed by serum uric acid levels of >420 µmol/L in males or >357 µmol/L in females. A total of 2585 hypertensive patients with complete data were included in the final statistical analysis. Totally 709 deaths (27.4%) occurred during the six-year follow-up, of which 475 deaths were attributable to cardiovascular disease (CVD). All-cause and CVD mortality of hypertensive patients with hyperuricemia was significantly higher than that of patients without hyperuricemia. The Cox regression analysis indicated that hazards ratios (HRs) of hyperuricemia for all-cause and CVD mortality were 1.206 (95% CI: 1.002-1.453) and 1.085 (95% CI: 1.002-1.271) respectively. All-cause and CVD mortality of hypertensive patients was significantly increased (both p < 0.05) when uric acid levels increased. HRs of uric acid levels >536 µmol/L to all-cause and CVD mortality of hypertensive patients were 2.115 (95% CI: 1.596-2.801) and 1.861 (95% CI: 1.296-2.673), respectively, compared with those of uric acid levels ≤357 µmol/L. CONCLUSIONS: The data from this cohort study indicate that hyperuricemia can predict increased all-cause and CVD mortality in hypertensive patients.


Assuntos
Hipertensão , Hiperuricemia , Ácido Úrico/sangue , Idoso , Causas de Morte , China/epidemiologia , Feminino , Humanos , Hipertensão/sangue , Hipertensão/complicações , Hipertensão/mortalidade , Hiperuricemia/sangue , Hiperuricemia/epidemiologia , Hiperuricemia/etiologia , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
15.
Int J Clin Exp Pathol ; 7(10): 6514-23, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25400729

RESUMO

An immerging role of TNF-α in collagen synthesis and cardiac fibrosis implies the significance of TNF-α production in the development of myocardial remodeling. Our previous study showed a reduction of TNF-α and attenuated cardiac remodeling in CXCR6 knockout (KO) mice after ischemia/reperfusion injury. However, the potential mechanism of TNF-α-mediated cardiac fibrosis with pressure overload has not been well elucidated. In the present study, we aim to investigate the role of CXCR6 in TNF-α release and myocardial remodeling in response to pressure overload. Pressure overload was performed by constriction of transverse aorta (TAC) surgery on CXCR6 KO mice and C57 wild-type (WT) counterparts. At 6 weeks after TAC, cardiac remodeling was assessed by echocardiography, cardiac TNF-α release and its type I receptor (TNFRI), were detected by ELISA and western blot, collagen genes Col1a1 (type I) and Col3a1 (type III) were examined by real-time PCR. Compared with CXCR6 WT mice, CXCR6 KO mice exhibited less cardiac dysfunction, reduced expression of TNFRI, Col1a1 and Col3a. In vitro, we confirmed that CXCR6 deficiency led to reduced homing and infiltration of CD11b(+) monocytes, which contributed to attenuated TNF-α release in myocardium. Furthermore, TNFRI antagonist pretreatment blocked AT1 receptor signaling and NOX4 expression, reduced collagen synthesis, and blunted the activity of MMP9 in CXCR6 WT mice after TAC, but these were not observed in CXCR6 KO mice. In the present work, we propose a mechanism that CXCR6 is essential for pressure overload-mediated myocardial recruitment of monocytes, which contributes to cardiac fibrosis through TNF-α-dependent MMP9 activation and collagen synthesis.


Assuntos
Quimiotaxia de Leucócito , Cardiopatias/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Monócitos/metabolismo , Miocárdio/metabolismo , Receptores CXCR/deficiência , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo , Remodelação Ventricular , Animais , Antígeno CD11b/metabolismo , Células Cultivadas , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Colágeno Tipo III/genética , Colágeno Tipo III/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Ativação Enzimática , Fibrose , Cardiopatias/genética , Cardiopatias/imunologia , Cardiopatias/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Monócitos/imunologia , Miocárdio/imunologia , Miocárdio/patologia , NADPH Oxidase 4 , NADPH Oxidases/metabolismo , Receptores CXCR/genética , Receptores CXCR6 , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo
16.
J Interv Card Electrophysiol ; 41(2): 169-75, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25227867

RESUMO

PURPOSE: This study aimed to assess pulmonary vein isolation (PVI) efficacy on atrial fibrillation (AF) recurrence and to determine a predictive dispersion of atrial refractoriness (dERP) value for performing PVI in paroxysmal supraventricular tachycardia (PSVT) patients. METHODS: Of 67 PSVT patients with past AF episodes who underwent accessory pathway (AP) or slow pathway of atrioventricular node ablation, 63 (4 lost to follow-up or death) were assigned into two groups (A and B; 29 and 34 patients, respectively) based on whether they underwent or not subsequent PVI, and all were followed-up up to 3 years. Atrial effective refractory period (AERP) and dERP were measured during the ablation procedure. RESULTS: In receiver operating characteristic (ROC) curve analysis, dERP = 74.5 ms effectively predicted AF recurrence in PSVT patients (p = 0.003). Difference in AF recurrence rate between groups did not reach statistical significance (17.2%, 5/29 vs. 29.4%, 10/34, p = 0.203). AF recurrence rate was lower in patients with dERP >74.5 ms who underwent AP or slow-pathway ablation with vs. without PVI (18.2%, 2/11 vs. 77.8%, 7/9, p = 0.012). CONCLUSIONS: PVI addition after successful AP or slow pathway of atrioventricular node ablation significantly reduced AF recurrence in PSVT patients with high atrial vulnerability (dERP >74.5 ms).


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Veias Pulmonares/cirurgia , Taquicardia Supraventricular/cirurgia , Adulto , Fibrilação Atrial/diagnóstico , Ablação por Cateter/efeitos adversos , Estudos de Coortes , Eletrocardiografia/métodos , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Recidiva , Medição de Risco , Taquicardia Supraventricular/diagnóstico , Fatores de Tempo , Resultado do Tratamento
18.
Ultrasound Med Biol ; 40(6): 1133-7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24613637

RESUMO

This study aimed to assess whether intra- and inter-atrial conduction delay could predict atrial fibrillation (AF) for paroxysmal supraventricular tachycardia (PSVT) patients after successful treatment by radiofrequency catheter ablation (RFCA). Echocardiography examination was performed on 524 consecutive PSVT patients (15 patients were excluded). Left atrial dimension, right atrial diameter and intra- and inter-atrial conduction delay were measured before ablation. Patients were divided into group A (n = 32): occurrence of AF after the ablation and group B (n = 477): remained in sinus rhythm during follow-up. Receiver operating characteristic (ROC) curve analysis was performed to estimate the predictive value of intra- and inter-atrial conduction delay. Both intra- and inter-atrial conduction delay were higher in group A than in group B (4.79 ± 0.30 msec vs. 4.56 ± 0.32 msec; 21.98 ± 1.32 msec vs. 20.01 ± 1.33; p < 0.05). Binary logistic regression analysis showed that intra- and inter-atrial conduction were significant influential factors for the occurrence of AF (odds ratio [OR] = 13.577, 95% confidence interval [CI], 3.469-48.914; OR = 2.569, 95% CI, 1.909-3.459, p < 0.05). The ROC cure analysis revealed that intra-atrial conduction delay ≥ 4.45 msec and inter-atrial conduction delay ≥ 20.65 were the most optimal cut-off value for predicting AF in PSVT patients after RFCA. In conclusion, this is the first study to show that the intra- and inter-atrial conduction delay could effectively predict AF in post-ablation PSVT patients.


Assuntos
Fibrilação Atrial/etiologia , Sistema de Condução Cardíaco/fisiopatologia , Taquicardia Supraventricular/cirurgia , Adolescente , Adulto , Idoso , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/fisiopatologia , Ablação por Cateter , Criança , Ecocardiografia , Eletrocardiografia , Feminino , Sistema de Condução Cardíaco/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Ondas de Rádio , Fatores de Risco , Taquicardia Supraventricular/diagnóstico por imagem , Taquicardia Supraventricular/fisiopatologia , Resultado do Tratamento
19.
Mol Cell Biochem ; 391(1-2): 259-66, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24639125

RESUMO

The aim of this study is to investigate the dynamic alterations of cardiac connexin 43 (Cx43), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in the setting of different ventricular fibrillation (VF) duration. In this study, thirty-two dogs were randomly divided into sham control group, 8-min VF group, 12-min VF group, and 30-min VF group. Cx43 and phosphorylated Cx43 (p-Cx43) in tissues were detected by western blot and immunofluorescence analysis. MMP-2 and TIMP-2 were detected by western blot and immunohistochemistry analysis. The results showed that Cx43 levels in three VF groups were significantly decreased compared with sham control group. p-Cx43 levels in 12-min and 30-min VF groups were significantly reduced compared with sham control group. The ratio of p-Cx43/Cx43 was also decreased in VF groups. Compared with sham controls, no significant difference was observed between the sham control group and 8-min VF group in MMP-2 level, but MMP-2 level increased in 12-min and 30-min VF groups. The ratios of MMP-2/TIMP-2 were higher in VF groups, and were correlated with the duration of VF. A remarkable correlation was observed between the ratio of p-Cx43/Cx43 and MMP-2/TIMP-2 (r = -0.93, P < 0.01). In conclusion, the alteration of Cx43 and/or p-Cx43 levels and the imbalance of MMP-2 and TIMP-2 may contribute to the initiation and/or persistence of VF. Maneuvers managed to modulate Cx43 level or normalize the balance of MMP-2/TIMP-2 are promising to ameliorate prognosis of VF.


Assuntos
Conexina 43/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Fibrilação Ventricular/enzimologia , Animais , Western Blotting , Modelos Animais de Doenças , Cães , Imunofluorescência , Fosforilação
20.
PLoS One ; 9(1): e85144, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24454806

RESUMO

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in the general population; yet, the precise mechanisms resulting in AF are not fully understood. Caveolin-1 (Cav-1), the principal structural component of caveolae organelles in cardiac fibroblasts, is involved in several cardiovascular conditions; however, the study on its function in atrium, in particular, in AF, is still lacking. This report examines the hypothesis that Cav-1 confers an anti-AF effect by mediating atrial structural remodeling through its anti-fibrotic action. We evaluated the expression of Cav-1, transforming growth factor-ß1 (TGF-ß1), and fibrosis in atrial specimens of 13 patients with AF and 10 subjects with sinus rhythm, and found that the expression of Cav-1 was significantly downregulated, whereas TGF-ß1 level, collagens I/III contents and atrial fibrosis were markedly increased, in AF. Western blot analysis demonstrated that treatment of human atrial fibroblasts (HAFs) with TGF-ß1 resulted in a concentration- and time-dependent repression of Cav-1. Downregulation of Cav-1 with siRNA increased the TGF-ß1-induced activation of Smad signal pathway and collagens production in HAFs. Furthermore, incubation of HAFs with the peptides derived from Cav-1 to achieve Cav-1 gain-of-function abolished the TGF-ß1-induced production of collagens I/III and decreases of MMP-2/-9 expression. Therefore it was concluded that Cav-1 is an important anti-AF signaling mediator by conferring its anti-fibrotic effects in atrium.


Assuntos
Fibrilação Atrial/metabolismo , Fibrilação Atrial/patologia , Caveolina 1/metabolismo , Fibroblastos/patologia , Átrios do Coração/patologia , Transdução de Sinais , Adulto , Idoso , Remodelamento Atrial/efeitos dos fármacos , Caveolina 1/química , Caveolina 1/deficiência , Caveolina 1/genética , Colágeno/biossíntese , Regulação para Baixo/efeitos dos fármacos , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/farmacologia , Estrutura Terciária de Proteína , RNA Interferente Pequeno/genética , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/farmacologia
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