Animal models of atherosclerosis

Abstract

An ideal animal model of atherosclerosis resembles human anatomy and pathophysiology and has the potential to be used in medical and pharmaceutical research to obtain results that can be extrapolated to human medicine. Moreover, it must be easy to acquire, can be maintained at a reasonable cost, is easy to handle and shares the topography of the lesions with humans. In general, animal models of atherosclerosis are based on accelerated plaque formation due to a cholesterol-rich/Western-type diet, manipulation of genes involved in the cholesterol metabolism, and the introduction of additional risk factors for atherosclerosis. Mouse and rabbit models have been mostly used, followed by pigs and non-human primates. Each of these models has its advantages and limitations. The mouse has become the predominant species to study experimental atherosclerosis because of its rapid reproduction, ease of genetic manipulation and its ability to monitor atherogenesis in a reasonable time frame. Both Apolipoprotein E deficient (ApoE) and LDL-receptor (LDLr) knockout mice have been frequently used, but also ApoE/LDLr double-knockout, ApoE3-Leiden and PCSK9-AAV mice are valuable tools in atherosclerosis research. However, a great challenge was the development of a model in which intra-plaque microvessels, haemorrhages, spontaneous atherosclerotic plaque ruptures, myocardial infarction and sudden death occur consistently. These features are present in ApoEFbn1 mice, which can be used as a validated model in pre-clinical studies to evaluate novel plaque-stabilizing drugs.

Fenretinide treatment accelerates atherosclerosis development in apoE‐deficient mice in spite of beneficial metabolic effects

“…In conclusion, all the above evidence demonstrate that fenretinide treatment, in spite of positive metabolic effects, severely altered blood cell turnover resulting in a worsening of atherosclerosis development in the main atherosclerosis-prone mouse model (Emini Veseli et al, 2017). Even if further investigations are required to demonstrate to what extent the above can be translated into the human setting, these results strongly suggest that careful selection and monitoring of patients undergoing fenretinide treatment is needed.…”

The Vascular Consequences of Metabolic Syndrome: Rodent Models, Endothelial Dysfunction, and Current Therapies

“…An ideal translational animal model for metabolic syndrome would closely resemble the human anatomy and pathophysiology of the disease (Emini Veseli et al, 2017). Thus, an important consideration when choosing an animal model is that it mimics the key clinical criteria that define metabolic syndrome.…”

“…Thus, HFD regimens are often combined with mice that are genetically dyslipidemic to incorporate the atherosclerotic phenotype in metabolic syndrome. For example, apolipoprotein Edeficient (ApoE −/− ) mice and low density lipoprotein receptor deficient (LDLR −/− ) mice show similar metabolic profiles to the diet-induced models described above, but have the added complication of advanced atherosclerosis (Emini Veseli et al, 2017).…”

Stanozolol promotes lipid deposition in the aorta through an imbalance in inflammatory cytokines and oxidative status in LDLr knockout mice fed a normal diet

“…Moreover, we did not use Western‐type diet to feed the animals, which could play a confounding role in our experiment . Although some similarity exists among our animal model and human beings, such as lipid profile and a slow atherosclerosis plaque formation, the extrapolation of our results to human beings should be done carefully, and clinical studies are necessary to confirm the finding in human beings.…”