Construction method of atherosclerosis vulnerable plaque mouse model

Abstract

The invention discloses a construction method of an atherosclerosis vulnerable plaque mouse model. According to the method, a low-density lipoprotein receptor gene (LDLR) with heterozygous point mutation in a fibrillin-1 (Fbn1) gene is obtained through a hybridization method to knock out a mouse. According to the method, Fbn1C1039G+/- point mutation is introduced into an LDLR-/- mouse genome for the first time, characteristics of two genotypes are combined, the method is simple and easy to implement, and vulnerable plaques with large lipid cores, a large number of inflammatory cells, typical thin fibrous caps, rich new blood vessels and the characteristics of plaque internal hemorrhage, vascular outward reconstruction and the like can be formed; the occurrence of acute cardiovascular and cerebrovascular events such as plaque rupture similar to that of the human body can be observed on the model. The method is high in model forming rate and good in repeatability, a good animal foundation is provided for medicine research and instrument consumable improvement, and a good platform is provided for exploring an atherosclerosis mechanism.

Description

technical field [0001] The invention relates to a method for constructing an artery model, in particular to a method for constructing an atherosclerotic vulnerable plaque mouse model. The invention belongs to the field of biotechnology. Background technique [0002] At present, the death of cardiovascular disease accounts for the first place in the total death causes of urban and rural residents in my country, and the disease burden of cardiovascular disease is increasing day by day, which has become a major public health problem. Coronary heart disease is the most important disease among cardiovascular diseases, and atherosclerosis (AS) is the most important pathological process of coronary heart disease. The research on atherosclerosis has become a research hotspot in the cardiovascular field in recent years. Vulnerable plaque rupture is the primary cause of adverse cardiovascular events. According to reports, 3 / 4 of acute myocardial infarctions are caused by plaque ruptu...

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Problems solved by technology

Vulnerable plaque rupture is the primary cause of adverse cardiovascular events. According to reports, 3/4 of acute myocardial infarctions are caused by plaque rupture. However, due to differences between animal genomes and human genomes, as well as plaque formation Different pathophysiological processes make the current vulnerable plaques in animal models very different from human vulnerable plaques. Therefore, the establishment of animal models similar to human atherosclerotic plaques has become an urgent problem to be solved

[0003] The research on atherosclerosis mainly has the following methods: 1. High-fat diet induction: Due to the difference in the genome of animals and humans, under the method of simple diet-induced atherosclerosis, animals such as mice and rabbits are less likely to develop atherosclerosis , only monkeys and pigs, which are highly homologous to human genomes, can produce human-like plaques, but such animals have problems such as expensive, long feeding time, and difficult operation, which have become the main limitations of research

2. Vascular injury: The time of plaque formation can be shortened by injuring the vascular endothelium, but its reproducibility is poor, and it cannot simulate the entire pathophysiological process of human plaque formation

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