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

Kunxiang He, Jinjie Wang, Haozhe Shi, Qiongyang Yu, Xin Zhang, Mengmeng Guo, Huijun Sun, Xiao Lin, Yue Wu, Luya Wang, Yuhui Wang, Xunde Xian, George Liu

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numberAJTR0086659
Pages (from-to)3116-3127
Number of pages12
JournalAmerican Journal of Translational Research
Volume11
Issue number5
StatePublished - Jan 1 2019

Keywords

  • Atherosclerosis
  • Familial hypercholesterolemia
  • Hamster
  • Low-density lipoprotein receptor
  • Mouse
  • Rat

ASJC Scopus subject areas

  • Molecular Medicine
  • Clinical Biochemistry
  • Cancer Research

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    He, K., Wang, J., Shi, H., Yu, Q., Zhang, X., Guo, M., Sun, H., Lin, X., Wu, Y., Wang, L., Wang, Y., Xian, X., & Liu, G. (2019). An interspecies study of lipid profiles and atherosclerosis in familial hypercholesterolemia animal models with low-density lipoprotein receptor deficiency. American Journal of Translational Research, 11(5), 3116-3127. [AJTR0086659].