RESUMO
Intermittent high glucose (IHG), one of the general and important symptoms of patients with diabetes, has greater effect than sustained high glucose on the development of diabetic cardiovascular complications, in which endothelial dysfunction caused by oxidative stress is regarded as the initiation. However, no study investigated either the degree of endothelial DNA oxidation caused by IHG or the potential protective effects of antioxidants. In this study, DNA oxidation, including 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentration and comet assay, was studied in human umbilical vein endothelial cells (HUVECs) under IHG with or without treatment of Ginkgo biloba extract (EGb 761). We found that high glucose, especially IHG, increased reactive oxygen species generation, 8-OHdG content and oxidative DNA damage in HUVECs. These high glucose-induced oxidative stress could be suppressed by EGb 761 (25-100 microg/ml) in a dose-dependent manner through the improvement of total antioxidant capacity. Our results indicated that the presence of significant DNA oxidation in HUVECs exposed to high glucose, and especially higher in the cells in IHG conditions. EGb 761, an antioxidant herbal medicine, can remarkably alleviate endothelial DNA oxidation caused by IHG, which may provide a novel approach for endothelial protection in the presence of IHG.
Assuntos
Dano ao DNA , Ginkgo biloba/química , Glucose/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Extratos Vegetais/farmacologia , 8-Hidroxi-2'-Desoxiguanosina , Antioxidantes/farmacologia , Linhagem Celular , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Eletroforese em Gel de Poliacrilamida , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , OxirreduçãoAssuntos
Doenças Cardiovasculares/complicações , Diabetes Mellitus/diagnóstico , Teste de Tolerância a Glucose , Glicemia , Isquemia Encefálica/complicações , Doenças Cardiovasculares/metabolismo , Testes Diagnósticos de Rotina , Humanos , Ataque Isquêmico Transitório/metabolismo , Medição de Risco , Acidente Vascular Cerebral/etiologiaRESUMO
Inflammation plays an important role in the pathophysiology of the metabolic syndrome (MS). We determined whether the overexpression of interleukin (IL)-18 could aggravate left ventricular (LV) remodeling and diastolic dysfunction in fructose-fed rats (FFRs). To create an animal model for MS, male Wistar rats received 10% fructose in water for 8 months. We used an adenovirus encoding rat IL-18 to overexpress IL-18 in FFRs by intravenous administration. IL-18 overexpression led to increases in collagen volume fraction and collagen deposition. LV systolic function was unaltered. But the LV end-diastolic pressure and the time constant of isovolumic relaxation (tau) were increased. Peak negative value of time derivative of LV pressure (-dp/dt) was decreased. Isovolumic relaxation time and myocardial index, as assessed by echocardiography, were increased. Overexpression of IL-18 leads to aggravated LV remodeling and dysfunction in FFRs. Attenuation of the inflammatory process may provide a novel therapeutic strategy in treating metabolic cardiomyopathy.
Assuntos
Cardiomiopatias/fisiopatologia , Insuficiência Cardíaca Diastólica/fisiopatologia , Interleucina-18/metabolismo , Disfunção Ventricular Esquerda/fisiopatologia , Animais , Cardiomiopatias/diagnóstico por imagem , Ecocardiografia , Fibrose/diagnóstico por imagem , Fibrose/metabolismo , Fibrose/fisiopatologia , Frutose/administração & dosagem , Frutose/metabolismo , Insuficiência Cardíaca Diastólica/diagnóstico por imagem , Masculino , Ratos , Ratos Wistar , Disfunção Ventricular Esquerda/diagnóstico por imagem , Remodelação VentricularRESUMO
BACKGROUND: Inflammation is an established risk factor for atherosclerosis. In an inflammatory state, nuclear factor-kappa B (NF-kappaB) is frequently activated as a key transcription activator for the downstream responses. HYPOTHESIS: The aim of this study was to investigate the changes of NF-kappaB in the aorta of patients with coronary atherosclerosis and its association with atherosclerotic risk factors. METHODS: From 2004 to 2005, we collected a small piece of ascending aorta in the bypass procedure from patients (n = 31) undergoing coronary artery bypass graft (CABG) surgery. The expression of NF-kappaB was determined by immunohistochemistry, and its transcriptional activity was evaluated by electrophoretic mobility shift assay. Celiac aortic tissues from 4 subjects without known atherosclerosis through the kidney donation program were taken as control. RESULTS: NF-kappaB was detectable in aortas from CABG patients with the transcriptional activities significantly increased. The relative level of aortic NF-kappaB expression was elevated in patients who were smokers or with hypertension. Spearman correlation revealed that aortic NF-kappaB expression had significant correlation with coronary severity scores (Gensini score, r = 0.608, P < .05). The NF-kappaB expression was positively correlated with the levels of blood glucose, low-density lipoprotein cholesterol, lipoprotein(a), total cholesterol, and non-high-density lipoprotein cholesterol (P < .05); but negatively correlated with high-density lipoprotein cholesterol (P < .05). CONCLUSIONS: Our study demonstrates a highly activated NF-kappaB in aortas from patients with coronary atherosclerosis, which may reflect overall arterial overinflammatory status. The findings of hyperactive NF-kappaB in aortas may provide a diagnostic parameter for the inflammation that is associated with and may cause atherosclerosis.
Assuntos
Aorta/metabolismo , Doença da Artéria Coronariana/metabolismo , NF-kappa B/metabolismo , Idoso , Aorta/patologia , Glicemia/análise , Colesterol/sangue , LDL-Colesterol/sangue , Ponte de Artéria Coronária , Doença da Artéria Coronariana/cirurgia , Feminino , Humanos , Hipertensão/metabolismo , Imuno-Histoquímica , Lipoproteína(a)/sangue , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fumar/metabolismoRESUMO
PURPOSE: To investigate the influence of angiotensin-converting enzyme inhibitor (ACEI) on cardiac innervation and inducible ventricular arrhythmias (VAs) in healed myocardial infarction (MI). METHODS: Left anterior descending coronary artery was ligated to induce MI in 30 rabbits. After oral captopril (10mg/kg/d) for 8 weeks, electrophysiological study was performed to evaluate the incidence of inducible VAs. RT-PCR and immunohistochemistry were used to measure the cardiac innervation. RESULTS: Eight weeks after the operation, the incidence of inducible VAs in the MI-placebo group was higher (58.3%, 7/12) than in the sham operation group (16.7%, 2/12, P < 0.05). However, the incidence of inducible VAs in the MI-captopril group was lower (27.2%, 3/11) than in the MI-placebo group (P < 0.05). Proliferation and growth of nerve fibres in the MI-placebo group were mainly distributed at the periphery of the infarcted and perivascular regions of the myocardium. The density of nerve fibres increased in the MI-placebo group (3889+/-521 microm2/mm2) compared with the sham group (1727+/-304 microm2/mm2, P < 0.01) at the infarct border. In the MI-captopril group, the density of nerve fibres (3507+/-433 microm2/mm2) at the infarct border did not differ from that in the MI-placebo group (P=0.07). MI-induced abnormal nerve fibre distribution was partly restored by captopril treatment. CONCLUSION: In this study, prolonged captopril treatment was effective in preventing VAs in healed MI, partly by attenuating the spatial heterogeneity of cardiac innervation.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Arritmias Cardíacas/tratamento farmacológico , Captopril/administração & dosagem , Ventrículos do Coração/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Fibras Nervosas/efeitos dos fármacos , Administração Oral , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Arritmias Cardíacas/patologia , Captopril/farmacologia , Eletrofisiologia , Ventrículos do Coração/inervação , Ventrículos do Coração/patologia , Imuno-Histoquímica , Infarto do Miocárdio/patologia , Fibras Nervosas/patologia , Placebos , Coelhos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de TempoRESUMO
AIM: To evaluate creatine kinase-MBmass (CK-MBmass) for the early diagnosis of infarct-related artery (IRA) patency after thrombolysis and the hierarchical diagnosis of related artery reperfusion (RAR). PATIENTS AND METHODS: CK-MBmass and creatine kinase-MBactivity (CK-MBactivity) were measured kinetically in 48 patients treated with thrombolysis and 96 patients treated with routine drugs. RESULTS: In the continuous-RAR (CRAR) group, the peak values of CK-MBmass and CK-MBactivity appeared at < or =12 h, the peak durations were maintained for < or =8 h before decreasing to normal at < or =42 h, which occurred more quickly than those values in the non-RAR (NRAR) group. In the temporary-RAR (TRAR) group, the peak values appeared at < or =12 h, but no significant differences were found between the TRAR and NRAR groups in the time that the peak durations lasted before decreasing to normal values. In the reobliteration group after RAR, the peak values appeared at < or =12 h, and the peak durations were maintained for < or =8 h. After returning to the normal, a second peak appeared, and the time required for the values to return to normal was prolonged significantly. CONCLUSIONS: CK-MBmass could be used as an indicator of RAR after thrombolysis; and the kinetic changes of serum CK-MBmass could be used for the hierarchical diagnosis of RAR in acute myocardial infarction.
Assuntos
Creatina Quinase Forma MB/sangue , Infarto do Miocárdio/tratamento farmacológico , Reperfusão Miocárdica , Terapia Trombolítica/métodos , Biomarcadores/sangue , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Neural remodeling is part of the pathophysiology of ventricular arrhythmias after myocardial infarction (MI). In this study, we developed a rabbit model of MI to investigate the effect of the beta-blocker metoprolol on ventricular neural remodeling and susceptibility to ventricular arrhythmias. METHODS: MI was induced by ligation of the left anterior descending coronary artery in 30 rabbits, and sham operations were performed in 12 control animals. Metoprolol was then administered to 15 of the MI animals. After electrophysiological recordings, the expression of nerve markers was studied at the infarct border and the non-infarct left ventricle free wall (LVFW) by immunostaining or RT-PCR. RESULTS: Eight weeks after MI, the incidence of inducible ventricular arrhythmias was significantly (P<0.01) higher in the MI group than in the sham group. However, metoprolol treatment decreased incidence of post-MI ventricular arrhythmias (8.3%) compared to those without treatment (58.3%, P<0.001). The density of nerve fibers was increased in MI group (3889+/-521 microm(2)/mm(2)) compared to the sham group (1727+/-304 microm(2)/mm(2)). Treatment of MI rabbits with metoprolol resulted in a partial reduction (2725+/-283 microm(2)/mm(2)). However, the shape and imbalance of nerve fibers appeared to be normalized by the metoprolol treatment. The expression levels of TH mRNA were reduced (P<0.01) by metoprolol treatment. CONCLUSION: Metoprolol reduces post-MI ventricular arrhythmias, partly by altering the neural remodeling process.
Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/prevenção & controle , Metoprolol/administração & dosagem , Infarto do Miocárdio/complicações , Remodelação Ventricular/efeitos dos fármacos , Animais , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/inervação , CoelhosRESUMO
Coupling factor 6 (CF6) is a novel endogenous inhibitor of prostacyclin. Plasma CF6 and 6-keto-PGF(1a) were measured by radioimmunoassay in 70 consecutively recruited patients with type 2 diabetes and in 56 healthy controls. A significantly increased plasma CF6 level was found in diabetics compared with controls. The CF6 level was inversely correlated with plasma 6-keto-PGF(1a) level and positively correlated with blood glucose and lipids. These results suggest that CF6 might be an obvious marker of impaired endothelium and might contribute to vascular damage in diabetes.