Animal Models of Atherosclerosis

Abstract

Atherosclerosis is a chronic inflammatory disorder that is the underlying cause of most cardiovascular disease. Both cells of the vessel wall and cells of the immune system participate in atherogenesis. This process is heavily influenced by plasma lipoproteins, genetics and the hemodynamics of the blood flow in the artery. A variety of small and large animal models have been used to study the atherogenic process. No model is ideal as each has its own advantages and limitations with respect to manipulation of the atherogenic process and modeling human atherosclerosis or lipoprotein profile. Useful large animal models include pigs, rabbits and non-human primates. Due in large part to the relative ease of genetic manipulation and the relatively short time frame for the development of atherosclerosis, murine models are currently the most extensively used. While not all aspects of murine atherosclerosis are identical to humans, studies using murine models have suggested potential biological processes and interactions that underlie this process. As it becomes clear that different factors may influence different stages of lesion development, the use of mouse models with the ability to turn on or delete proteins or cells in tissue specific and temporal manner will be very valuable.

Development of Aortic Valve Disease in Familial Hypercholesterolemic Swine: Implications for Elucidating Disease Etiology

“…Consistent with previous reports,25 evaluation of the coronary arteries of 2‐yo adult RFH swine revealed the presence of advanced atherosclerotic plaques (Figure 1). Invasion of smooth muscle cells, as detected by presence of αSMA, was observed within raised atheromatous regions (Figure 1D); these regions also exhibited evidence of increased lipid oxidation (Figure 1B).…”

“…Finally, the WT background for RFH swine was only recently developed, and this study used the most aged animals available from this herd. None of the previous publications describing the use of RFH swine as models for atherosclerosis and restenosis have included a background‐matched WT control 24, 25, 26, 27…”

[O2–04–01]: Clearance of Beta‐amyloid Is Facilitated by Apolipoprotein E and Circulating High‐density Lipoproteins in Bioengineered Human Vessels

“…Despite the tremendous wealth of knowledge generated from animal models, there are considerable challenges in translating these results into humans. For example, many AD risk genes have roles in various aspects of lipid metabolism, the most important of these being APOE (Giri et al, 2016), yet the innate physiological differences between murine and human lipoprotein metabolism (Getz and Reardon, 2012) may limit the predictive power of mouse model studies. Although it is well known that humans have three APOE allelic variants compared to the single Apoe allele in mice, and targeted replacement mice are available that express human APOE, there are also other important metabolic distinctions between mice and humans.…”

Hypercholesterolemia Induced Immune Response and Inflammation on Progression of Atherosclerosis in Apobtm2SgyLdlrtm1Her/J Mice

“…Animal models have provided valuable information on the sequential events and the mechanisms responsible for initiation and maturation of atherosclerotic lesions [3][4][5][6]. Apolipoprotein E deficient (ApoE−/−) and LDL receptor deficient (LDL-R−/−) mice are two hypercholesterolemic models used extensively in atherosclerosis research [7,8].…”