An interspecies study of lipid profiles and atherosclerosis in familial hypercholesterolemia animal models with low-density lipoprotein receptor deficiency

American Journal of Translational Research

Haozhe Shi¹  Xin Zhang²  Jinjie Wang³  Kunxiang He⁴  Qiongyang Yu⁵ 

[1] College of Pharmacy, Dalian Medical University, Dalian 116044, China;Department of Molecular Genetics, UT Southwestern Medical Center, Dallas 75390, Texas, USA;Hebei Invivo Biotech Co, Shijiazhuang, China;Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University, Beijing 100191, China;The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing An Zhen Hospital Affiliated to Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China

关键词: Mouse;    rat;    hamster;    low-density lipoprotein receptor;    familial hypercholesterolemia;    atherosclerosis;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Small rodents, especially mice and rats, have been widely used in atherosclerosis studies even though humans exhibit completely different lipoprotein metabolism and atherosclerotic characteristics. Until recently, various rodent models of human familial hypercholesterolemia (FH) have been created, including mice, rats, and golden Syrian hamsters. Although hamsters reportedly possess metabolic features similar to humans, there is no systematic characterization of the properties of circulating lipids and atherosclerotic lesions in these rodent models. We used three FH animal species (mice, rats, and hamsters) with low-density lipoprotein receptor (Ldlr) deficiency to fully assess lipoprotein metabolism and atherosclerotic characteristics. Compared to chow diet-fed mice and rats, Ldlr knockout (KO) hamsters showed increased cholesterols in LDL fractions similar to human FH patients. Upon 12-week high-cholesterol/high-fat diet feeding, both heterozygous and homozygous Ldlr KO hamsters displayed hyperlipidemic phenotypes, whereas only homozygous Ldlr KO mice and rats showed only moderate increases in plasma lipid levels. Moreover, rats were resistant to diet-induced atherosclerosis compared to mice, and hamsters showed more atherosclerotic lesions in the aortas and coronary arteries. Further morphological study revealed that only hamsters developed atherosclerosis in the abdominal segments, which is highly similar to FH patients. This unique animal model will provide insight into the translational study of human atherosclerosis and could be useful for developing novel treatments for FH patients.

【 授权许可】

CC BY-NC