RESUMO
BACKGROUND To examine changes of mRNA and protein expressions of MMP-2, Bcl-2, and BAX in atrial fibrillation (AF) patients, and investigate the correlations among these 3 biomarkers. MATERIAL AND METHODS Rheumatic heart disease patients (n=158) undergoing cardiac surgical procedures for mitral valve repair or replacement were included as the AF group (n=123), containing paroxysmal AF (n=42), persistent AF (n=36), and permanent AF (n=45). Rheumatic heart disease patients with sinus rhythm (SR) (n=35) were enrolled as the SR group (control group). Immunohistochemistry, Western blot, and real-time polymerase chain reaction (PCR) were applied to detect the protein and mRNA expression levels of MMP-2, Bcl-2, and BAX. Apoptosis was observed with light and electron microscopes and detected by TdT-mediated dUTP nick-end labeling (TUNEL). RESULTS Compared with the SR group, the left atrial diameters (LADs), protein and mRNA expression levels of MMP-2 and BAX, apoptotic index (AI), and Bcl-2/BAX ratio were evidently increased in the 3 AF groups, but protein and mRNA expression levels of Bcl-2 decreased in the AF groups (all P<0.05). Correlation analysis found that MMP-2 protein expression levels was positively correlated with BAX expression, but negatively correlated with Bcl-2 expression levels. CONCLUSIONS Our study results suggest that elevated MMP-2 expression and disturbance balance of Bcl-2/BAX expressions may be associated with the development and maintenance of AF. MMP-2 may be involved in the development of AF through promoting BAX expressions and inhibiting Bcl-2.
Assuntos
Fibrilação Atrial/enzimologia , Fibrilação Atrial/genética , Metaloproteinase 2 da Matriz/genética , Proteína X Associada a bcl-2/genética , Idoso , Apoptose , Arritmia Sinusal/enzimologia , Arritmia Sinusal/genética , Arritmia Sinusal/patologia , Fibrilação Atrial/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Miócitos Cardíacos/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
Phosphodiesterases PDE2, PDE3, and PDE4 are expressed in murine sinoatrial cells. PDE3 and/or PDE4 reduce heart rate but apparently do not influence the tachycardia mediated through sinoatrial ß1- and ß2-adrenoceptors despite the high content of sinoatrial cAMP. The function of PDE2 is, however, uncertain. Prostaglandin PGE1 elicits sinoatrial tachycardia through EP receptors, but the control by phosphodiesterases is unknown. We investigated on spontaneously beating right atria of mice the effects of the PDE2 inhibitors Bay 60-7550 and EHNA on basal beating and the tachycardia produced by noradrenaline (3 nM) and PGE1 (1 µM). Bay 60-7550 (1 µM), but not EHNA (10 µM), increased basal sinoatrial beating. EHNA also failed to produce tachycardia in the presence of the adenosine deaminase inhibitor 2'-deoxycoformycin (10 µM), remaining inconclusive whether PDE2 reduces basal sinoatrial beating. Rolipram (10 µM) and cilostamide (300 nM) caused moderate tachycardia. The tachycardia evoked by Bay 60-7550 was similar in the absence and presence of rolipram. Noradrenaline elicited stable tachycardia that was not increased by Bay 60-7550. A stable tachycardia caused by PGE1 was not increased by the inhibitors of PDE2, PDE3, and PDE4. Unlike PDE3 and PDE4 which reduce murine basal sinoatrial beating, a possible effect of PDE2 needs further research. The stable tachycardia produced by noradrenaline and PGE1, together with the lack potentiation by the inhibitors of PDE2, PDE3, and PDE4, suggests that cAMP generated at the receptor compartments is hardly hydrolyzed by these phophodiesterases. Evidence from human volunteers is consistent with this proposal.
Assuntos
Alprostadil , Arritmia Sinusal/induzido quimicamente , Nucleotídeo Cíclico Fosfodiesterase do Tipo 2/antagonistas & inibidores , Frequência Cardíaca/efeitos dos fármacos , Norepinefrina , Inibidores da Fosfodiesterase 3/farmacologia , Inibidores da Fosfodiesterase 4/farmacologia , Taquicardia Supraventricular/induzido quimicamente , Animais , Arritmia Sinusal/enzimologia , Arritmia Sinusal/fisiopatologia , AMP Cíclico/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 2/metabolismo , Modelos Animais de Doenças , Hidrólise , Preparação de Coração Isolado , Masculino , Camundongos , Inibidores da Fosfodiesterase 3/toxicidade , Inibidores da Fosfodiesterase 4/toxicidade , Receptores Adrenérgicos beta 1/metabolismo , Receptores de Prostaglandina E/metabolismo , Sistemas do Segundo Mensageiro/efeitos dos fármacos , Taquicardia Supraventricular/enzimologia , Taquicardia Supraventricular/fisiopatologia , Fatores de TempoRESUMO
1. Clinical and experimental evidence suggest that changes in the autonomic tone play a role in the pathogenesis of atrial fibrillation. 2. We have studied the distribution of molecular forms of acetylcholinesterase (AChE) in atrial biopsies obtained from individuals without arrhythmias and in patients with atrial fibrillation. 3. Analysis of the distribution of globular and asymmetric AChE forms, showed a decrease in the amount of the globular forms of biopsies taken from atria during fibrillation. 4. This study is the first attempt to characterize the molecular forms of AChE in the human heart of patients with sinus rhythm and chronic atrial fibrillation.
