Alteration Of Cx43, Cx45 In Acute Myocardial Infarction After Transplantation Of Mesenchymal Stem Cells

Background Acute myocardial infarction(AMI) is a vary dangerous disease which have high case-fatality rate so to be payed close attention in the world . Gap junction (GJ) ,bening composed of connexins (Cx),is a specialized membrane structures consisting of arrays of intercellular channels that directly connect adjacent cells by providing chemical and electrical communication. Cx43 is the major gap junction protein in the adult mammalian ventricle, and Cx45 is a gap junction protein that exprsses at special areas in ventricle such as conducting system. Cx43 and Cx45 plays important roles in connective communications.Electrical signal conduction and normaI rhythmic contraction of myoca rdial cells.In infarcted myocardium, the total amount of Cx43 was reduced and the distribution of Cx43 gap junctions was markly disturbed. These changes form the anatomical basis for conduction block, anisotropy and reentry arrhythmias. Recent researches found that Cx45 may regulate the change of Cx43 in ischemic heart disease.Although medical ways nowadays such as arteria coranaria interventional therapy and coronary artery bypass surgery can establish reperfusion, necrotic myocardiums can not regenerate, which can lead to heart failure and death. Mesenchymal stem cells (MSCs) have a potential of multi-differentiation and characters of easy-gain and remarkable amplification. Recent researches show that MSCs can regenerate necrotic myocardiums,promote expression of Cx43 snd improve blood supply. Animal studies and clinical research manifest that is a new pathway in the therapy of AMI,which make them be the hot spot of research on the treatment of myocardial infarction.Objectives To investigate the alterations of Cx43 and Cx45 expression and their distribution after acute myocardial infarction and transplantation of allogenic MSCs in rats.Methods Wistar rats were randomly divided into Normal group, Sham gorup, MI group and MSCs group. Each group was then divided into 3 subgroups according to 4, 8 and 12w post-transplantation. The AMI were established by ligation of the left anterior descending (LAD) of coronary artery. Rat hears with AMI were transplante of MSCs. Immunofluorescence laser scanning confocal microscopy (LSCM) and electromicroscope were used to detect the Cx43and Cx45.Results (1) LSCM found that DAPI-labeled MSCs distributed widely at the host ischemic zone and formed Cx43 gap junction with the host. (2)Immunofluorescence and immuno-electron microscope showed that Cx43 reduced significantly at ischemic zone in 4, 8 and 12w post-transplantation in MI group. Comparing to MI group, Cx43 expression was statistically higher in MSCs group. There was no difference of Cx43 expression at infarct zone between MI group and MSCs group. Cx45 increased significantly on ischemic zone at 4, 8 and 12w post-transplantation in MI group. Comparing to MI group, Cx45 expression was statistically lower in MSCs group. There was no difference of Cx45 expression at infarct zone between MI group and MSCs group.(3)Coexpression zones of Cx43/Cx45 may be found in MI groups of ischemic area at 8w and 12w post-transplantation. No any coexpression zones of Cx43/Cx45 could be found in MI groups and MSCs groups of normal area at 4, 8 and 12w post-transplantation.Conclusions(1)Acute myocardial infarction can induce the Alteration of Cx43 and Cx45, such as Cx43 protein decrease, Cx45 protein increase and Cx43/Cx45 regional coexpression.(2)MSCs can survive at the host ischemic zone and expressed Cx43.(3)Transplantation of Mesenchymal Stem Cells can modulate the alteration of Cx43 and Cx45.