Effect Of Extracellular Matrix(ECM)Metabolism On Pathogenesis Of Abdominal Aortic Aneurysm

Effect of Extracellular Matrix(ECM) Metabolism on Pathogenesis of abdominal aortic aneurysmABSTRACTBackgroundAbdominal aortic aneurysm(AAA) seriously threatens human health. Despite the fact that advances in modern surgical treatment of the disease have produced significantly improved results, the operative mortality rate of traditional open surgery is still 3-5%, so the optimal management of small abdominal aortic aneurysms is controversial, some recommend early surgery, and others recommend ultrasound scan surveillance unless a large threshold size is reached or rapid expansion occurs. Now a novel approach to this disease, namely, endovascular grafting exclusion(EVGE) has brought hope to improvement the security of the surgical treatment, but the long term results of this technique is uncertain for the aneurysm neck dilatation after operation. Recently, the study on pathogenesis of AAA told us, that aneurysmal dilatation is accompanied bu a marked loss of elastin from the tunica media, and the elastase, collagenase, and gelatinase activities with in the aneurysmal aortic wall was increased. These new findings have brought hope to retard the aneurysm growth with medical or gene therapy.However, Few reports have appeared as to the role of elastin and collagen degradation in the early stage of aneurysmal dilatation, either home or abroad. Moreover, no specific action of MMP and its inhibitor in aortic aneurysm is available presently.To investigate the roles of elastin and collagen degradation in the early stage of aneurysmal dilatation and the specific hydrolytic enzyme of elastin and collagen, we decided to construct animal model of abdominal aortic aneurysm, and to observe the changes of elastin, collagen and MMP continuously.M th ds:1. Elastase-induced animal model of abdominal aortic aneurysms in rats.1) A 1-vcm segment of the abdominal aorta of male wiater rats was isolated and perfused with 2ml pancreatic elastase, animals were killed 2 weeks later2) The whole abdominal aorta was then removed and embedded in paraffin for histological and morphological examination.2. Content and turnover of elastin and collagen in experimental animal model.1) The abdominal aortas were harvested in postoperative day 2,day 7,and day 14, the diameters of aorta were measurment.2) The aortic sections were stained for elastin and collagen.3) Histology studies were performed to analyze changes in elastin and collagen with computer image analysis3. Study of the matrix metallproteinases in rat abdominal aortic aneurysms on protein level1) Forty male Wistar rats were divided into two groups randomly, the rats of study group were perfused with pancreatic elastase in the isolated abdominal aorta to construct the rat model of AAA.2) Laparotomy was preformed on 14th day after operation, the aortas were measured and harvested. The rats of control group were operated and the aortas were harvested immediately.3) Immunohistologic coloration and computer image analysis were performed to analyze the contents and distributing of MMP-2 and MMP-9.Results:1. The aortic diameter progress to aneurysmal dimension in high concentration elastase group. Histology study revealed loss of elastin in media of the aorta in the high concentration elastase group. Neither macroscopic nor microscopic lesions were founded in low elastase group and control group.2. Computer image analysis of aortic sections revealed loss of elastin and collagen in tunica media of the aorta in the study group. There is a negtive correlation between the dilatation rate of the aorta and the concentration of theelastin(r=0.91).3. Immunohistology study revealed the MMP contents in AAA exceeding normal aorta obviously. The MMP-2 cotents in AAA tunica media is higher-5-than MMP-9.Conclusions:1. Direct infusion of pancreatic elastase into across-clamped segment of the rat aorta can induce aneurysm model with similarities to aneurysms of human abdominal aorta.2. There is a signi...