The Relationship Between APOC3 Overexpression Mice And Elastase Induced Abdominal Aortic Aneurysms

Objective: Abdominal aortic aneurysms(AAAs) are characterized by structural degeneration of the aortic wall and progressive aortic dilatation, which usually lead to inflammatory responses. The most common causes of AAAs include aging, smoking, family history, hyperlipidemia hypercholesterolemia, etc. Apolipoprotein C3(APOC3), a major component of VLDLs, is important in regulating triglycerides, as increased expression levels of APOC3 lead to elevated triglycerides levels. It was reported that APOC3 plays critical roles in the development of ischemic vascular diseases and coronary diseases. However, the relationship between APOC3 and AAAs is still unclear.In this study, we employed APOC3 overexpression transgenic mice(APOC3-OE) to test the hypothesis that over expressing APOC3 exacerbates the development of AAAs. AAA mouse model was created by extraluminal porcine pancreatic elastase exposure.Methods:APOC3-OE mice and littermate wild-type(WT) controls(8 to 12-week-old) were undergone elastase extraluminal application to the infrarenal abdominal aorta. The application of elastase was performed under abdominal cavity anesthesia with 5% chloral hydrate. The mice were sacrificed after collecting blood sample from angular vein 14 days after surgery. Then the aorta was harvested and separated for preparing sections. We used TC kits and TG kits to detect the lipid levels. HE-staining shows the morphological changes of abdominal aorta. EVG-staining shows the destruction of elastin. The expression levels of interleukin-6(IL-6) and matrix metalloproteinase-9(MMP-9), a member of matrix metalloproteinase(MMP) family, were assessed by immunohistochemical approaches.Result1 Plasma lipid levels increased significantly in APOC3-OE mice.Total cholesterol(TC) level of WT mice is 87.3 ± 18.8 mg/dl, the triglyceride(TG) level is 96.3 ± 21.7 mg/dl, the TC level of APOC3-OE mice is 214.0 ± 58.3 mg/dl and the TG level is 1070.0 ± 291.6 mg/dl.2 Elastase induced abdominal aortic aneurysms display a significant increase elastin destruction in APOC3-OE mice.The aortic dilation appeared on the segment between renal artery and lilac artery branch after surgery for 14 days. Compared with WT, vascular elastic fibers were destroyed more severely in APOC3-OE mice.3 The expression of IL-6 was increased in the model of APOC3-OE mice.Immunohistochemical staining showed that IL-6 was rarely detected in the elastase--treated vascular area in WT mice. Compared with WT mice, IL-6 expression in the aneurysm of APOC3-OE mice increased by 3.21-fold(P< 0.05).4 The expression level of MMP-9 was increased in the aneurysm model of APOC3-OE mice.In WT mice, MMP-9 was rarely detected in the elastase--treated area. MMP-9 was accumulated in the adcentitia area, increased by 2.94-fold in APOC3-OE mice, compared with WT mice(P < 0.05).Conclusions:1 The damage of the AAAs in APOC3-OE mice is more severe than that of WT mice.2 The expression levels of inflammation-related proteins are significantly increased in the abdominal aortic aneurysms of APOC3-OE mice, compared with WT mice.3 Overexpression of APOC3 exacerbates the development of AAAs. Results:...