A method for constructing an atherosclerotic vulnerable plaque mouse model

Abstract

The invention discloses a method for constructing an atherosclerotic vulnerable plaque mouse model. The method is to obtain a low-density lipoprotein receptor gene (LDLR) knockout mouse with a heterozygous point mutation of the fibrillin 1 (Fibrillin-1, Fbn1) gene by crossing. The present invention for the first time Fbn1 C1039G+ / ‑ Point mutations introduced into LDLR ‑ / ‑ Mouse genome, combining the characteristics of the two genotypes, the method is simple and easy, and can form a large lipid core, a large number of inflammatory cells, a typical thin fibrous cap, abundant new blood vessels and intraplaque hemorrhage, outward remodeling of blood vessels, etc. The characteristic vulnerable plaque, and it can be observed in the model that it is similar to human plaque rupture, which leads to the occurrence of acute cardiovascular and cerebrovascular events. It has a high molding rate and good repeatability, providing a good animal basis for drug research and improvement of device consumables, and a good platform for exploring the mechanism of atherosclerosis.

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...

AI Technical Summary

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

Gene knockout mice currently widely used for atherosclerosis include: ApoE - / - Mice and LDLR - / - Mice, etc., under normal diet, ApoE - / - Mice can also form atherosclerotic plaques, but the degree of atherosclerosis is mild, and ApoE fed a high-fat diet - / - and LDLR - / - Mice can form atherosclerotic plaques, but their plaque formation is rapid, and it is difficult to observe the outward remodeling seen in human vulnerable plaques

Based on the above limitations, some researchers have used gene knockout technology to construct ApoE gene knockout dogs (publication number is CN106987604). This method has the advantage of retaining the primary symptoms of the disease, and the disease phenotype lasts for a long time. However, due to the long feeding time of dogs, Problems such as slow reproduction are not conducive to general research

However, the vulnerable plaque model established by the method of using liquid nitrogen to freeze blood vessels provided by the patent application with the publication number CN101480359A is not conducive to studying the mechanism of vulnerable plaques and exploring intervention methods

[0004] In summary, the current research on atherosclerotic vulnerable plaques lacks an animal model and modeling method consistent with the characteristics of human vulnerable plaques

Images