Genomic and Transcriptomic Analysis of Hypercholesterolemic Rabbits: Progress and Perspectives

Abstract

Rabbits (Oryctolagus cuniculus) are one of the most widely used animal models for the study of human lipid metabolism and atherosclerosis because they are more sensitive to a cholesterol diet than other experimental animals such as rodents. Currently, two hypercholesterolemic rabbit models are frequently used for atherosclerosis studies. One is a cholesterol-fed wild-type rabbit and the other is the Watanabe heritable hyperlipidemic (WHHL) rabbit, which is genetically deficient in low density lipoprotein (LDL) receptor function. Wild-type rabbits can be easily induced to develop severe hypercholesterolemia with a cholesterol-rich diet due to the marked increase in hepatically and intestinally derived remnant lipoproteins, called β-very low density lipoproteins (VLDL), which are rich in cholesteryl esters. WHHL rabbits are characterized by elevated plasma LDL levels on a standard chow diet, which resembles human familial hypercholesterolemia. Therefore, both rabbit models develop aortic and coronary atherosclerosis, but the elevated plasma cholesterol levels are caused by completely different mechanisms. In addition, cholesterol-fed rabbits but not WHHL rabbits exhibit different degrees of hepatosteatosis. Recently, we along with others have shown that there are many differentially expressed genes in the atherosclerotic lesions and livers of cholesterol-fed rabbits that are either significantly up- or down-regulated, compared with those in normal rabbits, including genes involved in the regulation of inflammation and lipid metabolism. Therefore, dietary cholesterol plays an important role not only in hypercholesterolemia and atherosclerosis but also in hepatosteatosis. In this review, we make an overview of the recent progress in genomic and transcriptomic analyses of hypercholesterolemic rabbits. These transcriptomic profiling data should provide novel insight into the relationship between hypercholesterolemia and atherosclerosis or hepatic dysfunction caused by dietary cholesterol.

Unveiling ncRNA regulatory axes in atherosclerosis progression

“…Thus, there is an urgent need to develop a more personalized medicine, and to enhance patient care through improved diagnostic sensitivity with more effective interventions in ATH prevention and treatment [4]. In this sense, years of research on the genomic basis of ATH have provided the biomedical community with a knowledge of gene‐related ATH risk factors, such as SNPs [5,6], genes and gene variants [7–9], alterations in DNA methylation [10,11], changes in gene expression [12,13], etc. Nevertheless, in the last years a new player has entered the game of disease‐associated genes: the highly heterogeneous group of non‐coding RNAs, which are progressively becoming important factors for atherosclerosis (and other diseases) research either as biomarkers of disease progression or as pathophysiological intermediates, while their operative interactions highlight the remarkable structural and functional complexity of the human genome.…”

RecombinantLactococcus lactisExpressing Ling Zhi 8 Protein Ameliorates Nonalcoholic Fatty Liver and Early Atherogenesis in Cholesterol-Fed Rabbits

“…e authors reported that NAFLD was consistently associated with coronary artery soft plaque, suggesting early atherosclerosis [5]. ere are many etiological and pathological similarities between atherosclerosis and NAFLD, including hypercholesteremia and hypertriglyceridemia, which lead to lipid deposition in tissue and cause inflammation and fibrosis [6,7].…”

The History of the WHHL Rabbit, an Animal Model of Familial Hypercholesterolemia (I) - Contribution to the Elucidation of the Pathophysiology of Human Hypercholesterolemia and Coronary Heart Disease -

“…Rabbit genome information is now available from the National Center for Biotechnology Information database at http://www.ncbi.nlm.nih.gov/sra, and a comprehensive database containing both rabbit genome and transcriptome information has been comprehensively constructed by the Chinese Academy of Sciences 73) at http://www.picb.ac.cn/RabGTD/. Fan et al 74) identified 29.8 million single nucleotide polymorphisms and 1.6 million small indels in the 30 genomes in WHHLMI rabbits in the above rabbit genome analyses, suggesting the difficulty in the detection of the gene(s) associated with the progression of coronary lesions and the development of myocardial infarction in WHHLMI rabbits.…”