Dietary Cholesterol Exacerbates Statin-Induced Hepatic Toxicity in Syrian Golden Hamsters and in Patients in an Observational Cohort Study

Yu, Qiongyang; Ma, Xiaochi; Wang, Yunan; Shi, Haozhe; An, Jian; Wang, Yuhui; Dong, Zhen; Lu, Yijing; Ge, Junbo; Liu, George; Xia, Xian; Sun, Aijun

doi:10.1007/s10557-020-07060-3

Cited by 6 publications

(4 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, after 4 weeks of high cholesterol diet, the weight gain rate of HCD group, SIM group, and OGAG‐H group was significantly lower than that of the control group. Statins have been reported to have toxic side effects on the muscles and liver, such as significantly reduced food intake, weight loss, and liver damage (Yu et al., 2021; Yves et al., 1990). Therefore, it is speculated that the lower weight gain rate of HCD group, SIM group, and OGAG‐H group than CON group may also had been caused by liver damage of zebrafish after cholesterol or SIM treatment or high‐dose OGAG‐H treatment.…”

Section: Discussionmentioning

confidence: 99%

Glycosaminoglycan from Ostrea rivularis attenuates hyperlipidemia and regulates gut microbiota in high‐cholesterol diet‐fed zebrafish

Kong

Liu

Dai

et al. 2021

Food Science & Nutrition

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Glycosaminoglycan from Ostrea rivularis attenuates hyperlipidemia and regulates gut microbiota in high‐cholesterol diet‐fed zebrafish

Kong

Liu

Dai

et al. 2021

Food Science & Nutrition

View full text Add to dashboard Cite

show abstract

“…Further, lipid-lowering drugs had differing effects on hamsters to mice and rats. Inhibition of cholesterol synthesis by statins was very toxic in the hamster, especially when fed a cholesterol-rich diet ( 11 , 15 , 16 ). Moreover, inhibition of cholesterol absorption by ezetimibe completely reversed the increased plasma lipid levels in hamsters fed atherogenic diets, and this effect was not altered by a compensatory increase in cholesterol synthesis ( 9 , 17 , 18 ).…”

Section: Introductionmentioning

confidence: 99%

Dietary-Induced Elevations of Triglyceride-Rich Lipoproteins Promote Atherosclerosis in the Low-Density Lipoprotein Receptor Knockout Syrian Golden Hamster

Xiao

Yang

et al. 2021

Front. Cardiovasc. Med.

Self Cite

View full text Add to dashboard Cite

Elevated triglycerides are associated with an increased risk of cardiovascular disease (CVD). Therefore, it is very important to understand the metabolism of triglyceride-rich lipoproteins (TRLs) and their atherogenic role in animal models. Using low-density lipoprotein receptor knockout (LDLR−/−) Syrian golden hamsters, this study showed that unlike LDLR−/− mice, when LDLR−/− hamsters were fed a high cholesterol high-fat diet (HFD), they had very high plasma levels of triglycerides and cholesterol. We found that LDLR−/− hamsters exhibited increased serum TRLs and the ApoB100 and 48 in these particles after being fed with HFD. Treatment with ezetimibe for 2 weeks decreased these large particles but not the LDL. In addition, ezetimibe simultaneously reduced ApoB48 and ApoE in plasma and TRLs. The expression of LRP1 did not change in the liver. These findings suggested that the significantly reduced large particles were mainly chylomicron remnants, and further, the remnants were mainly cleared by the LDL receptor in hamsters. After 40 days on an HFD, LDLR−/− hamsters had accelerated aortic atherosclerosis, accompanied by severe fatty liver, and ezetimibe treatment reduced the consequences of hyperlipidemia. Compared with the serum from LDLR−/− hamsters, that from ezetimibe-treated LDLR−/− hamsters decreased the expression of vascular adhesion factors in vascular endothelial cells and lipid uptake by macrophages. Our results suggested that in the LDLR−/− hamster model, intestinally-derived lipoprotein remnants are highly atherogenic and the inflammatory response of the endothelium and foam cells from macrophages triggered atherosclerosis. The LDL receptor might be very important for chylomicrons remnant clearance in the Syrian golden hamster, and this may not be compensated by another pathway. We suggest that the LDLR−/− hamster is a good model for the study of TRLs-related diseases as it mimics more complex hyperlipidemia.

show abstract

“…Nearly 99.1% of genes (21,193) found in the Syrian hamster were functionally annotated (Table S3 and the lengths of the average gene and coding sequence (CDS) were predicted as 33,298.04bp and 1,459.84bp, respectively. The results were consistent with the distribution of gene features in other rodents (Table 2).…”

Section: Genome Assembly Of Syrian Hamstermentioning

confidence: 99%

“…Although the mouse is a common model animal for studying atherosclerosis-related diseases, the natural genetic divergence between mouse and human limits its power in certain scenarios, such as when investigating key metabolic enzyme defects and genetic background differences [16][17][18]. Compared with mice, the low cost and fast growth rate of Syrian hamsters has advanced its application in experimental studies [19][20][21]. More notably, the cardiomyopathic Syrian hamster shows a physical response to a high fat/cholesterol diet in a similar manner to humans, with high levels of atherogenic lipoproteins observed under these feeding conditions [22].…”

Section: Introductionmentioning

confidence: 99%

Genomic-transcriptomic analysis reveals Syrian hamster as a superior human disease animal model

Wang,

Cheng

et al. 2024

Preprint

View full text Add to dashboard Cite

Backgroud: The Syrian hamster (Mesocricetus auratus) has shown promise as a human diseases model, recapitulating features of different human diseases including the emerging COVID-19. However, the landscape of its genome and transcriptome has not been systematically dissected, restricting its potential applications. Results: Here we provide a complete analysis of the genome and transcriptome of the Syrian hamster and found that its lineage diverged from that of the Chinese hamster (Cricetulus griseus) around 29.4 million years ago. 21,387 protein-coding genes were identified, with 90.03% of the 2.56G base pair sequence being anchored to 22 chromosomes. The further comparison of the transcriptomes from 15 tissues of the Syrian hamster disclosed that Syrian hamster shares a pattern of alternative splicing modes more similar to humans, compared to rats and mice. A integrated genomic-transcriptomic analysis revealed that Syrian hamster also has genetic and biological advantages as a superior animal model for cardiovascular diseases. Strikingly, several genes involved in SARS-COV-2 infection including ACE2present a higher homology with humans than other rodents and show the same function as the human counterparts. Conclusion: The detailed molecular characterisation of the Syrian hamster in the present study opens a wealth of fundamental resources from this small rodent for future research into human disease pathology and treatment.

show abstract

Dietary Cholesterol Exacerbates Statin-Induced Hepatic Toxicity in Syrian Golden Hamsters and in Patients in an Observational Cohort Study

Cited by 6 publications

References 30 publications

Glycosaminoglycan from Ostrea rivularis attenuates hyperlipidemia and regulates gut microbiota in high‐cholesterol diet‐fed zebrafish

Glycosaminoglycan from Ostrea rivularis attenuates hyperlipidemia and regulates gut microbiota in high‐cholesterol diet‐fed zebrafish

Dietary-Induced Elevations of Triglyceride-Rich Lipoproteins Promote Atherosclerosis in the Low-Density Lipoprotein Receptor Knockout Syrian Golden Hamster

Genomic-transcriptomic analysis reveals Syrian hamster as a superior human disease animal model

Contact Info

Product

Resources

About