TY - JOUR
T1 - An interspecies study of lipid profiles and atherosclerosis in familial hypercholesterolemia animal models with low-density lipoprotein receptor deficiency
AU - He, Kunxiang
AU - Wang, Jinjie
AU - Shi, Haozhe
AU - Yu, Qiongyang
AU - Zhang, Xin
AU - Guo, Mengmeng
AU - Sun, Huijun
AU - Lin, Xiao
AU - Wu, Yue
AU - Wang, Luya
AU - Wang, Yuhui
AU - Xian, Xunde
AU - Liu, George
N1 - Funding Information:
NSFC 31520103909 and 81270367 to G.L., NSFC81570787 to Y.W.; National Key Research and Development Program of China (2016YF-E0126000) to Y.W. G.L. is a fellow at the Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University.
Funding Information:
NSFC 31520103909 and 81270367 to G.L., NSFC 81570787 to Y.W.; National Key Research and Development Program of China (2016YF-E0126000) to Y.W. G.L. is a fellow at the Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University.
Publisher Copyright:
© 2019, E-Century Publishing Corporation. All rights reserved.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Atherosclerosis
KW - Familial hypercholesterolemia
KW - Hamster
KW - Low-density lipoprotein receptor
KW - Mouse
KW - Rat
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M3 - Article
AN - SCOPUS:85067350095
SN - 1943-8141
VL - 11
SP - 3116
EP - 3127
JO - American Journal of Translational Research
JF - American Journal of Translational Research
IS - 5
M1 - AJTR0086659
ER -