The Study Of Matrix Metalloproteinase-2,-9 And Tissue Inhibitor Of Metalloproteinase-2 Expression In Acute Ascending Aortic Dissection

PartⅠThe Pathological Changes of Vascular Smooth Muscle Cells in Acute Ascending Aortic Dissectionobjective:Study the pathological changes occured in the aortic wall of acute ascending aortic dissection(AAD),especially that of vascular smooth muscle cells(VSMC).Method:Acute AAD samples(n=35) taken during aortic replacement operation within 72 hours from onset of dissection and the control aortic samples(n=21) from donar hearts were investigated by electron microscopy,hematoxylin-eosin(H-E) staining and Mallory staining.Result:Histopathologic findings consisted of combinations of elastin fragmentation, medial degeneration,and aortic wall fibrosis.The dissected aortas had an intimal tear which led to the outer media,and with fresh thrombus occasionally attached. Macrophages and lymphocytes sometimes infiltrated the dissected medial edge, however,these cells were absent in the adjacent intact wall.Fragmentation and attenuation of the elastic lamella were noticeable in the media of the dissected aorta but not in the control aortic wall.Under electron microscopy,the extracellular matrix(ECM) was sparse in the dissected aortic interlamellar space.VSMCs were the main cellular component in the medial layer of the aortic wall.Contractile-type and synthetic-type VSMCs were intermingled in the dissected aortic wall.In addition,the basement membrane of the VSMC was usually thin and often lacking in the dissected aortic wall.The media of the ascending aorta of the control cases consisted mainly of contractile-type VSMCs with the basement membrane showing normal thickness. Degenerative elastic lamellae and spiraled collagen were rarely observed in the control aorta. Conclusion:It could be observed that the VSMCs from the dissected aorta had a vigorous synthetic function,with basement membrane destruction or elimination.The elastin fragmentation,aortic wall fibrosis,and ECM rarefaction could also be found in the dissected aortas.PartⅡThe Matrix Metalloproteinase-9 Expression in the Acute Ascending Aortic Dissection and the Influential Factors ExplorationObjective:To explore the expression of matrix metalloproteinase-9(MMP-9) in human AAD,assessing the correlation between MMP-9 expression and VSMC pathologies,and analyzing the influential factors of the MMP-9 expression.Method:The immunohistochemical staining of MMP-9 was carried out and semiquantified by staining intensity analysis.The correlation of hypertension, smoking and aneurysm diameter with the expression of MMP-9 was discussed.The MMP-9 expression in aortic tissue was also investigated by Western blotting.Result:VSMC was the main cell type that expressed MMP-9.The expression of MMP-9 elevated significantly in dissected group compared with the control group (P＜0.001),and also,MMP-9 expression had a positive correlation with a history of hypertension(P＜0.01) or a great aneurysm diameter(P＜0.05).Conclusion:The increased expression of MMP-9 induced by elevated blood pressure led to fragmentation of elastin and destruction of the aortic wall.The pathological matrix secreation and deposition in the aortic wall made the wall inflexible and decreased the wall strength.It can be speculated that the aortic dissection occured while the hemodynamic stress acting on an aneurysm exceeded its wall strength. PartⅢThe Expression of Matrix Metalloproteinase-2 and Tissue Inhibitor of Metalloproteinase-2 in Acute Ascending Aortic DissectionObjective:To evaluate the expressions of MMP-2 and tissue inhibitor of metalloproteinase(TIMP)-2 in acute AAD.Methods:Acute AAD samples(n=35) taken during aortic replacement operation within 72 hours from onset of dissection and the control aortic samples(n=21) taken from the donar hearts were investigate.The immunohistochemical staining of MMP-2 and TIMP-2 was carried out for all aortic samples and semiquantified by staining intensity analysis.The MMP-2 and TIMP-2 expression in aortic tissue was also investigated by Western blotting.Results:The expression of MMP-2 and TIMP-2 was mainly in the cytoplasm of VSMCs.The expression of TIMP-2 increased significantly(P＜0.05) in the dissected group compared with the control group.There was no difference in the expression of MMP-2 between the two groups(P＞0.05).The results of Western blotting consistent with that of immunohistochemical staining.Conclusious:The increased expression of TIMP-2 and unchanged expression of MMP-2 might account for the occurrence of acute AAD and indicate the tissue remodelling occurred in the dissected aortic wall.