MicroRNA30a Regulates The Expression Of Lysyl Oxidase In Thoracic Aorta And Relates To Mechanism Of Thoracic Aortic Dissection

Objective:Acute aortic dissection is of great mortality and the mechanism of the lethal disease is still not fully revealed.LOX(lysyl oxidase)is a critical protein of extracellular matrix and essential link protein in maintaining the functional structure of media of aorta,and also regulate the secretion of cytokines in smooth muscle cell.Loss of LOX may play an important role in developing acute aortic dissection.To evaluate the the relationship between pathogenesis of aortic dissection and LOX which is a key cross-link protein in ECM and play an important role in maintain the proper structure of elastin by examine the expression of LOX and relative proteins in human specimen.Lentiviral vector was used to transfect both in cell level and rat to regulate the expression of miR30 a.And observe the difference of the expression of LOX and relative proteins as well as the successful rate of establishing the acute aortic dissection animal model and aim to explore how the miR30a-LOX axis works in the mechanism of aortic dissection.Method: Human Aortic tissue specimen(aortic dissection group/control group)was obtained during the operation on acute aortic dissection(n=18)and trimming the donor heart(n=5).Slides were stained using EVG method and immuohistochemical stain by anti-LOX/anti-elastin and anti-collagen antibody.The slides were scanned at 20 X magnification using a Scan Scope XT digital slide scanner to create whole-slide image data files at 0.5?m/pixel resolution and viewed using Image Scope software.Western-blot was also introduced to validate the difference between aortic dissection group and control group.Also,rt PCT was used to evaluate the difference of miR30 a between the two groups.SD male rats were divide into 5 groups(blank group/BAPN&Ang II/BAPN&Ang II up-regulated miR30a/BAPN&Ang II down-regulated miR30a/BAPN&Ang II empty vector).Acute aortic dissection model in rats was established by Ang II infusion to BAPN-treated rats which were feeded BAPN from 3weeks after born at a dose of 1g/kg/day till 7 weeks,then Ang II was infused by Alzet pump at a dose of 1?g/kg/min.Angiography and aortic CTA were performed to identify the different successful ratio of establishing aortic dissection model.After rats were executed the aortic tissue was harvested rt PCT ? western-blot as well as specific immunoreactive stain were applied to observe the difference of the expression of miR30a?LOX and relative proteins.Results: MiR30 a were down-regulated in the aortic dissection group.Significant difference of expression of LOX and relative proteins was observed(P<0.05)between aortic dissection group and control group when analysed by Image Pro software.Compared with other groups miR30 a up-regulated group had a significant higher rate of establishing the acute aortic dissection model LOX and relative proteins had a significant decrease.Conclusion: miR30a-LOX axis exists in aortic tissue and miR30a/29 b play an important role in the mechanism of the develop of acute aortic dissection.