Establishment And Phenotyping Of Atherosclerotic Model Of ApoE Knockout Bama Pigs

Background: With the increasing incidence of cardiovascular disease,atherosclerosis,which is the underlying cause of cardiovascular and cerebrovascular diseases,has also received widespread attention.In the early stage of atherosclerosis,the intimal and subendocardial lipids and carbohydrates of the arterial wall were abnormally aggregated,and the vascular endothelial bulge formed atherosclerotic lesions or fibrous lipid lesions,resulting in thickening of the vascular wall and narrowing of the lumen.As the disease progresses,the atherosclerotic plaque will rupture and the ruptured plaque will fall off.As the blood flow enters the circulation,a thrombus forms in the stenosis of the lumen,blocking blood flow.Apolipoprotein E(Apo E)protein is an important protein in lipid metabolism.The loss of Apo E function leads to disorders of lipid metabolism and accelerates the progression of atherosclerosis.Many scientists use Apo E transgenic mice as an animal model for atherosclerosis studies,but Apo E knockout mice do not well mimic the etiology and course of atherosclerosis in humans,so establishing a suitable atherosclerosis model for Atherosclerosis research is essential.The laboratory successfully developed Apo E knockout pigs in 2016.The pig’s cardiovascular system and apolipoproteins are extremely similar to humans.They are more suitable for simulating the course of atherosclerosis in humans than rodents,knocking out the Apo E gene.It will accelerate the occurrence and development of atherosclerosis.This large animal model can lay the foundation for the study of atherosclerosis.Objective: To cultivate Apo E knockout pigs and induce atherosclerotic lesions,establish the first international atherosclerosis Apo E gene knockout pig model,so as to better simulate the development of human atherosclerosis,and help scientific research Workers studied the mechanism of atherosclerotic lesions in greater depth and accumulated important research data for the early detection of atherosclerotic lesions.Methods: Western Blot was used to detect the expression of Apo E protein in newborn piglets;blood lipid data of each piglet were measured before fed with high fat diet,and the differences were analyzed;feeding high fat diet to accelerate atherosclerosis in Apo E knockout pigs The incidence rate,during the feeding process,the blood lipid levels in each piglet were measured and the progress of the modeling was evaluated.Western Blot was used to detect the expression of Apo E and Apo B in high-fat fed piglets,and the incidence of atherosclerosis in Apo E knockout piglets was detected by oil red and H&E staining.Results: Apo E-knockout pigs were successfully induced atherosclerotic lesions and severe hyperlipidemia six months after high-fat diet.The Apo E knockout was compared with the previous model.The cloned pig model has the characteristics of rapid onset and stable disease,which can provide a large number of research data for the future research on atherosclerosis.