Cargando…
Dietary Cholesterol Is Highly Associated with Severity of Hyperlipidemia and Atherosclerotic Lesions in Heterozygous LDLR-Deficient Hamsters
Objective: Familial hypercholesterolemia (FH) is a dominant inherited disease caused mainly by low-density lipoprotein receptor (LDLR) gene mutations. To different extents, both heterozygous and homozygous FH patients develop premature coronary heart disease (CHD). However, most of the experimental...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678973/ https://www.ncbi.nlm.nih.gov/pubmed/31323736 http://dx.doi.org/10.3390/ijms20143515 |
_version_ | 1783441229235617792 |
---|---|
author | Wang, Jinjie He, Kunxiang Yang, Chun Lin, Xiao Zhang, Xin Wang, Yuhui Liu, George Xian, Xunde |
author_facet | Wang, Jinjie He, Kunxiang Yang, Chun Lin, Xiao Zhang, Xin Wang, Yuhui Liu, George Xian, Xunde |
author_sort | Wang, Jinjie |
collection | PubMed |
description | Objective: Familial hypercholesterolemia (FH) is a dominant inherited disease caused mainly by low-density lipoprotein receptor (LDLR) gene mutations. To different extents, both heterozygous and homozygous FH patients develop premature coronary heart disease (CHD). However, most of the experimental animal models with LDLR deficiency could not fully recapitulate FH because they develop hyperlipidemia and atherosclerosis only in homozygous, but not in heterozygous, form. In the current study, we investigated the responsiveness of the LDLR+/− hamster to dietary cholesterol and whether plasma cholesterol levels were positively associated with the severity of atherosclerosis. Approach and Methods: wild type WT and LDLR+/− hamsters were fed a high fat diet with different cholesterol contents (HCHF) for 12 or 16 weeks. Plasma lipids, (apo)lipoproteins, and atherosclerosis in both the aorta and coronary arteries were analyzed. After a HCHF diet challenge, the levels of total cholesterol (TC) in WT and LDLR+/− hamsters were significantly elevated, but the latter showed a more pronounced lipoprotein profile, with higher cholesterol levels that were positively correlated with dietary cholesterol contents. The LDLR+/− hamsters also showed accelerated atherosclerotic lesions in the aorta and coronary arteries, whereas only mild aortic lesions were observed in WT hamsters. Conclusions: Our findings demonstrate that, unlike other rodent animals, the levels of plasma cholesterol in hamsters can be significantly modulated by the intervention of dietary cholesterol, which were closely associated with severity of atherosclerosis in LDLR+/− hamsters, suggesting that the LDLR+/− hamster is an ideal animal model for FH and has great potential in the study of FH and atherosclerosis-related CHD. |
format | Online Article Text |
id | pubmed-6678973 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-66789732019-08-19 Dietary Cholesterol Is Highly Associated with Severity of Hyperlipidemia and Atherosclerotic Lesions in Heterozygous LDLR-Deficient Hamsters Wang, Jinjie He, Kunxiang Yang, Chun Lin, Xiao Zhang, Xin Wang, Yuhui Liu, George Xian, Xunde Int J Mol Sci Communication Objective: Familial hypercholesterolemia (FH) is a dominant inherited disease caused mainly by low-density lipoprotein receptor (LDLR) gene mutations. To different extents, both heterozygous and homozygous FH patients develop premature coronary heart disease (CHD). However, most of the experimental animal models with LDLR deficiency could not fully recapitulate FH because they develop hyperlipidemia and atherosclerosis only in homozygous, but not in heterozygous, form. In the current study, we investigated the responsiveness of the LDLR+/− hamster to dietary cholesterol and whether plasma cholesterol levels were positively associated with the severity of atherosclerosis. Approach and Methods: wild type WT and LDLR+/− hamsters were fed a high fat diet with different cholesterol contents (HCHF) for 12 or 16 weeks. Plasma lipids, (apo)lipoproteins, and atherosclerosis in both the aorta and coronary arteries were analyzed. After a HCHF diet challenge, the levels of total cholesterol (TC) in WT and LDLR+/− hamsters were significantly elevated, but the latter showed a more pronounced lipoprotein profile, with higher cholesterol levels that were positively correlated with dietary cholesterol contents. The LDLR+/− hamsters also showed accelerated atherosclerotic lesions in the aorta and coronary arteries, whereas only mild aortic lesions were observed in WT hamsters. Conclusions: Our findings demonstrate that, unlike other rodent animals, the levels of plasma cholesterol in hamsters can be significantly modulated by the intervention of dietary cholesterol, which were closely associated with severity of atherosclerosis in LDLR+/− hamsters, suggesting that the LDLR+/− hamster is an ideal animal model for FH and has great potential in the study of FH and atherosclerosis-related CHD. MDPI 2019-07-18 /pmc/articles/PMC6678973/ /pubmed/31323736 http://dx.doi.org/10.3390/ijms20143515 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Wang, Jinjie He, Kunxiang Yang, Chun Lin, Xiao Zhang, Xin Wang, Yuhui Liu, George Xian, Xunde Dietary Cholesterol Is Highly Associated with Severity of Hyperlipidemia and Atherosclerotic Lesions in Heterozygous LDLR-Deficient Hamsters |
title | Dietary Cholesterol Is Highly Associated with Severity of Hyperlipidemia and Atherosclerotic Lesions in Heterozygous LDLR-Deficient Hamsters |
title_full | Dietary Cholesterol Is Highly Associated with Severity of Hyperlipidemia and Atherosclerotic Lesions in Heterozygous LDLR-Deficient Hamsters |
title_fullStr | Dietary Cholesterol Is Highly Associated with Severity of Hyperlipidemia and Atherosclerotic Lesions in Heterozygous LDLR-Deficient Hamsters |
title_full_unstemmed | Dietary Cholesterol Is Highly Associated with Severity of Hyperlipidemia and Atherosclerotic Lesions in Heterozygous LDLR-Deficient Hamsters |
title_short | Dietary Cholesterol Is Highly Associated with Severity of Hyperlipidemia and Atherosclerotic Lesions in Heterozygous LDLR-Deficient Hamsters |
title_sort | dietary cholesterol is highly associated with severity of hyperlipidemia and atherosclerotic lesions in heterozygous ldlr-deficient hamsters |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678973/ https://www.ncbi.nlm.nih.gov/pubmed/31323736 http://dx.doi.org/10.3390/ijms20143515 |
work_keys_str_mv | AT wangjinjie dietarycholesterolishighlyassociatedwithseverityofhyperlipidemiaandatheroscleroticlesionsinheterozygousldlrdeficienthamsters AT hekunxiang dietarycholesterolishighlyassociatedwithseverityofhyperlipidemiaandatheroscleroticlesionsinheterozygousldlrdeficienthamsters AT yangchun dietarycholesterolishighlyassociatedwithseverityofhyperlipidemiaandatheroscleroticlesionsinheterozygousldlrdeficienthamsters AT linxiao dietarycholesterolishighlyassociatedwithseverityofhyperlipidemiaandatheroscleroticlesionsinheterozygousldlrdeficienthamsters AT zhangxin dietarycholesterolishighlyassociatedwithseverityofhyperlipidemiaandatheroscleroticlesionsinheterozygousldlrdeficienthamsters AT wangyuhui dietarycholesterolishighlyassociatedwithseverityofhyperlipidemiaandatheroscleroticlesionsinheterozygousldlrdeficienthamsters AT liugeorge dietarycholesterolishighlyassociatedwithseverityofhyperlipidemiaandatheroscleroticlesionsinheterozygousldlrdeficienthamsters AT xianxunde dietarycholesterolishighlyassociatedwithseverityofhyperlipidemiaandatheroscleroticlesionsinheterozygousldlrdeficienthamsters |