Yet, the failure of therapeutic treatment for the patients with lipid disorders and atherosclerosis in different clinical trials demonstrates that the favorable results and theories from mouse study need to be revisited when they are translated into human disease because mice cannot completely mimic the metabolic profiles of humans. Genetically-engineered mouse models with lipid disorders provide valuable insights into the mechanisms of lipid metabolism and atherosclerosis based on the similarities of mouse genes to those risk genes identified by human genome-wide association study (GWAS), extrapolating the findings using mouse models to human study. Over the past 40 years, mouse models have been widely used for human atherosclerosis study due to the advantages of low cost and ease of maintenance and manipulation. Therefore, targeting dyslipidemia has been proposed to be a promising treatment for atherosclerosis. To our knowledge, familial hypercholesterolemia (FH) with elevated low density lipoprotein-cholesterol (LDL-C), familial hypertriglyceridemia with increased triglyceride and familial low high density lipoprotein-cholesterol (HDL-C) are 3 common rare diseases with dysfunctional mutations in genes involved in lipid regulation, which have been reported to be independent strong risk factors of atherosclerosis. The former can be easily corrected through dietary adjustment and increased physical activity however, the latter is difficult to normalize through environmental intervention, in which pharmaceutical treatment or even gene therapy will be required. Dyslipidemia is classically caused by environmental factors and genetic factors. However, inasmuch as CVD, especially atherosclerosis-related CVD (ASCVD), is multifactorial disease, the incomplete understanding of human atherosclerosis limits the development of therapeutic approaches for clinical trials.Īlthough there are many risk factors influencing the progress of atherosclerosis, to date, the relationship between dyslipidemia and atherosclerosis has been well documented, suggesting that dyslipidemia is an important culprit of atherosclerosis. Given the burden of CVD and its devastating consequence of national public health, considerable efforts have been made to study the molecular mechanisms underlying the pathogenesis of CVD. In China, the epidemiological evidence shows that the prevalence of CVD has been increasing continuously, contributing to –45% of death based on the China Cardiovascular Disease Report 2018.
The purpose of this review was to summarize the genetically-modified hamster models with dyslipidemia to date, and their potential applications and perspective for ASCVD.Ītherosclerosis, a chronic inflammatory disease leading to the occlusion of arteries by atherosclerotic plaques, is a major pathological basis of cardiovascular disease (CVD), including coronary heart disease, stroke and peripheral vascular disease, which is the first leading cause of morbidity and mortality worldwide.
With the development and breakthrough of novel gene editing technology, Syrian golden hamster, a small rodent animal replicating the metabolic characteristics of humans, has been genetically modified, suggesting that gene-targeted hamster models will provide new insights into the precision medicine and translational research of ASCVD. However, based on the concept of precision medicine and high demand of translational research, the applications of mouse models for human ASCVD study would be limited due to the natural differences in metabolic features between mice and humans even though they are still the most powerful tools in this research field, indicating that other species with biological similarity to humans need to be considered for studying ASCVD in future. Over the past 40 years, small rodent animals, such as mice, have been widely used for understanding of human atherosclerosis-related cardiovascular disease (ASCVD) with the advantages of low cost and ease of maintenance and manipulation. Cardiovascular disease is the leading cause of morbidity and mortality in both developed and developing countries, in which atherosclerosis triggered by dyslipidemia is the major pathological basis.
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