The Study Of Expression Of Connexin40 And Connexin43 In Atrial Myocardium In Patients With Coronary Heart Disease And The Role In Atrial Fibrillation Pathological Mechanism

Background:Atrial fibrillation is a kind of supraventricular arrhythmia which is a complete absence of coordinated atrial systole.commonly encountered arrhythmia. The mechanism of onset and maintenance of atrial fibrillation is not fully understood, though many recent studies have allowed improvements in the comprehension of the pathophysiology of the arrhythmia. For onset of atrial fibrillation, some researches on mechanism of onset dicovered the focal discharge could resulted in paroxysm AF in the vena cava system such as the vena coronaria, the superior and inferior vena cava and pulmonary vena. Besides, an increase in sympathetic tone, cardiac fat pad and vascular nerves in chambers heart is considered by many researchers as an important factor in initiating and maintaining atrial fibrillation, which first result in atrial premature beats, paroxysmal atrial tachycardia by diminish autorhythmic cell membrance potential, after-depolarization and triggers. For maintenance of atrial fibrillation, many recent studies have allowed atrial remodeling is the important reentry substrate of atrial fibrillation, which include atrial electroical remodeling and atrial anatomical remodeling. In current literatural, atrial fibrillation is generally subdivided into two forms:lone and pathological atrial fibrillation. Dilated left atrial has been considered to be one of the major factors linked to inducibility and persistence of pathological atrial fibrillation.Atrial enlargement may be related to both the multiple re-entrant circuits and electrophysiological characteristics of the atrial myocardium. In fact, all of myocardium is involved in any type of arrhythmia (including AF); arrhythmia is no fewer determined by passive current conduction than membrane channels. Accounting for AF is incomplete regardless of passive conduction between cells. It has been proved that gap junction is the only base structure responsible for intercellular current conduction. Gap junction is a specialized regions of the membranes of adjacent cells, containing arrays of densely packed intercellular channels that directly connect the cytoplasmic compartments of neighboring cells and permit ihtercellular passage of ions and small molecules. Gap junctions maintain cellular homeostasis by allowing communication between adjacent cells. In the heart, gap junctions provide the pathways for intercellular current flow, enabling coordinated action potential propagation. Gap-junctional channels are constructed from connexins (Cxs), a multigene family of conserved proteins termed connexins. In the mammalian heart, Single gap junction channel is composed of six connexin that abbreviate Cx by the molecular weight of the specific protein. It has been established that mammalian cardiac express Cx31.9, Cx37, Cx40, Cx43and Cx45. but different tissue of the heart express different amounts and combinations of these connexins, Cx43 was confirmed to be abundantly in all four chambers in human heart, Cx45 expression appears to be within the atrioventricular conduction system and Cx40 is present specifically in the atrium and in the specialized conducting system. Studies have shown that the changes of ionic concentration, ionic channel activities and phosphorylation have involved by the initiation of atrial fibrillation in a few seconds or minutes, and the expression changes of mRNA and proteins,including connexins, take place in several hours or days later. Structural changes are present in atrial fibrillation including atrium myocytes hypertrophia, apoptosis, inflammatory cell infiltrate and interstitial fibrosis.Cx40 gap junction channel was speculated to play critical roles in atria arrhythmia and AF. Although there are a few of researches about Cx40 and Cx43 on mechanisms of rheumatic heart disease AF, there are few reports about the changes of Cx40 and Cx43 expression, spatial distribution patern, and their morphology in human atrial myocardium from coronary heart disease. Our study composed of three parts aim to reveal the expression of Cx40, Cx40mRNA, Cx43, Cx43mRNA and the disorganization of connexin40 in the atrium myocardium of patients with coronary heart disease,, which to probe the mechanisms of atrial fibrillation in coronary heart disease. Objective:To explore the expression of Cx40mRNA,Cx40 in atrium myocardium of patients suffering from coronary heart disease with or without artial dilated or atrial fibrillation.Methods:26 patients with Coronary heart disease and 11 patients with rheumatic heart disease undergoing cardiac surgery for coronary artery bypass graft were involved in this study and were divided into four groups according to the atrial size and rhythm. All patients were examined by coronary arteriongraphy, echocardiogram and ECG before surgical operation.11 cases with AF and left atrial dilatation(AF+LAD),8 with sinus rhythm and left atrial dilatation (SR+LAD),7 sinus rhythm without atrial dilatation (SR) and 11 cases with AF and right artial dilatation(AF+RAD). Expression of Cx40mRNA was detected by RT-PCR. Expression of Cx40 was detected by immunoblotting assay(western blot).Results: 1. Significantly decreased were observed in the Cx40mRNA,Cx40 expression in atrium myocardium in all of the atrial dilatation groups (P <0.05).2. No obvious changes were observed in the Cx40mRNA,Cx40 expression in AF+LAD group and SR+LAD group(P> 0.05).3. Comparing with the Cx40mRNA,Cx40 expression in right atrium of the SR group, AF+LAD group and SR+LAD group, there was significantly decreased than that in the left atrium in AF+LAD group and SR+LAD group(P< 0.01).Conclusion:The decrease expression of Cx40mRNA,Cx40 is relation with left atrial dilatation, the decrease expression of Cx40mRNA,Cx40 and left atrial dilatation could be an important agents in the occurrence and maintenance of AF. Objective:To explore the effects of connexin 43mRNA and connexin 43 and the left atrium size in the AF by studying the expression of Connexin43mRNA and connexin 43 in Atrium of patients suffering from coronary heart disease with or without AF.Methods:26 patients with Coronary heart disease and 11 patients with rheumatic heart disease undergoing cardiac surgery for coronary artery bypass graft were involved in this study and were divided into four groups according to the atrial size and rhythm.11 cases with AF and left atrial dilatation (AF+LAD),8 with sinus rhythm and left atrial dilatation (SR+LAD),7 sinus rhythm without atrial dilatation (SR) and 11 cases with AF and right artial dilatation(AF+RAD). Expression of Cx43mRNA was detected by RT-PCR. Expression of Cx43 was detected by immunoblotting assay(western blot).Results:No obvious change was observed in the Cx43mRNA and Cx43 expression in dilated atrial myocytes in the four groups (P> 0.05). Conclusion:The expression of Cx43mRNA and Cx43 is not relation with left atrial dilatation and the expression of Cx43mRNA and Cx43 contribute less than the expression of Cx40 in the occurrence and maintenance of AF. Objective:The labelled samples were examined using a confocal microscope and light microscope to explore the anatomical structure of dilated atrium in the patients with coronary heart disease.Methods:26 patients with Coronary heart disease and 11 patients with rheumatic heart disease undergoing cardiac surgery for coronary artery bypass graft were involved in this study and were divided into four groups according to the atrial size and rhythm.11 cases with AF and left atrial dilatation (AF+LAD),8 with sinus rhythm and left atrial dilatation (SR+LAD),7 sinus rhythm without atrial dilatation (SR) and 11 cases with AF and right artial dilatation(AF+RAD). The spatial distribution pattern of Cx40 were detected through light microscope and confocal lasers canning microscopy assay.Results:1.The results revealed atrial anatomical remodeling have involved in the dilatation of atrial myocytes.2.Myolysis, glucogen aggregation, fibrosis, cytochondriom change and nuclear depolymerize have been observed by confocal microscope in dilated atrial myocytes.3. Adipose infiltration, hypertrophia, nuclear multiplication, nuclear atypia and interstitial fibrosis have been observed by light confocalConclusion:Atrial anatomical remodeling have involved in the dilatation of atrial myocytes which could be an important agent in the recurrence formation of AF.