Biomaterial Database

Hyperlipidemia induces typical atherosclerosis development in Ldlr and Apoe deficient rats. 2018

Yongliang Zhao, and Yiqing Yang, and Roumei Xing, and Xueqin Cui, and Yufang Xiao, and Ling Xie, and Panpan You, and Tongtong Wang, and Li Zeng, and Wenhui Peng, and Dali Li, and Huaqing Chen, and Mingyao Liu

Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, China.

Low-density lipoprotein receptor (Ldlr) and apolipoprotein E (Apoe) knockout (KO) mice have been widely used as animal models of atherosclerosis. However, data suggested that it is difficult to develop typical atherosclerosis in rats. To this end, Ldlr and Apoe KO rats were generated and the potential to develop novel atherosclerosis models was evaluated. We established Apoe/Ldlr single and double KO (DKO) rats via the CRISPR/Cas9 system in the same background. Phenotypes of dyslipidemia and atherosclerosis in these KO rats were systematically characterized. Knockout of either gene led to severe dyslipidemia and liver steatosis. Significant atherosclerotic plaques were observed in the abdominal aorta of all mutant rats fed a normal diet for 48 weeks. Western diet greatly aggravated atherosclerosis and fatty liver. In addition, we found mononuclear cell infiltration in early lesions. Increased expression of inflammatory cytokines, as well as macrophage accumulation in lesions of mutants, was observed, indicating that mononuclear cell trafficking and endothelial inflammation affected atherogenesis. Moreover, mutant rats displayed a sex difference profile more similar to humans in which males had heavier plaque burdens than females. Deficiency of either Ldlr or Apoe genes induced hyperlipidemia, which promoted endothelial inflammation and led to typical atherosclerosis in rats on normal or Western diets. These models display certain advantages, which will benefit future investigations of atherosclerotic pathology and antiatherosclerotic therapeutics.

UI	MeSH Term	Description	Entries
D006949	Hyperlipidemias	Conditions with excess LIPIDS in the blood.	Hyperlipemia,Hyperlipidemia,Lipemia,Lipidemia,Hyperlipemias,Lipemias,Lipidemias
D008297	Male		Males
D010641	Phenotype	The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.	Phenotypes
D011973	Receptors, LDL	Receptors on the plasma membrane of nonhepatic cells that specifically bind LDL. The receptors are localized in specialized regions called coated pits. Hypercholesteremia is caused by an allelic genetic defect of three types: 1, receptors do not bind to LDL; 2, there is reduced binding of LDL; and 3, there is normal binding but no internalization of LDL. In consequence, entry of cholesterol esters into the cell is impaired and the intracellular feedback by cholesterol on 3-hydroxy-3-methylglutaryl CoA reductase is lacking.	LDL Receptors,Lipoprotein LDL Receptors,Receptors, Low Density Lipoprotein,LDL Receptor,LDL Receptors, Lipoprotein,Low Density Lipoprotein Receptor,Low Density Lipoprotein Receptors,Receptors, Lipoprotein, LDL,Receptor, LDL,Receptors, Lipoprotein LDL
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004730	Endothelium, Vascular	Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.	Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D005234	Fatty Liver	Lipid infiltration of the hepatic parenchymal cells resulting in a yellow-colored liver. The abnormal lipid accumulation is usually in the form of TRIGLYCERIDES, either as a single large droplet or multiple small droplets. Fatty liver is caused by an imbalance in the metabolism of FATTY ACIDS.	Liver Steatosis,Steatohepatitis,Steatosis of Liver,Visceral Steatosis,Liver Steatoses,Liver, Fatty,Steatohepatitides,Steatoses, Liver,Steatoses, Visceral,Steatosis, Liver,Steatosis, Visceral,Visceral Steatoses
D005260	Female		Females
D000072669	Gene Editing	Genetic engineering or molecular biology techniques that involve DNA REPAIR mechanisms for incorporating site-specific modifications into a cell's genome.	Base Editing,Genome Editing,Editing, Base,Editing, Gene,Editing, Genome
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia