Mouse Models for Atherosclerosis Research—Which Is My Line?

Abstract

Atherosclerosis is one of the primary causes of cardiovascular disease and mortality. This chronic immunometabolic disease evolves during decades in humans and encompasses different organs and immune cell types, as well as local and systemic processes that promote the progression of the disease. The most frequently used animal model to study these atherogenic processes and inter-organ crosstalk in a short time frame are genetically modified mouse models. Some models have been used throughout the last decades, and some others been developed recently. These models have important differences in cholesterol and lipoprotein metabolism, reverse cholesterol transport pathway, obesity and diabetes as well as inflammatory processes. Therefore, the disease develops and progresses differently in the various mouse models. Since atherosclerosis is a multifaceted disease and many processes contribute to its progression, the choice of the right mouse model is important to study specific aspects of the disease. We will describe the different mouse models and provide a roadmap to facilitate current and future atherosclerosis researchers to choose the right model depending on their scientific question.

Research Models for Studying Vascular Calcification

“…Hyperlipidemia in one of the main triggering factors in the pathophysiology of human atherosclerosis. In mice, the lipoprotein profile significantly differs from humans [167,168]. Mice are lacking the cholesteryl ester transfer protein, an enzyme that transfers cholesterol from high-density lipoprotein (HDL) to apolipoprotein B-containing lipoproteins as low-density lipoprotein (LDL) and very low-density particles (VLDL) [169].…”

“…Mice are lacking the cholesteryl ester transfer protein, an enzyme that transfers cholesterol from high-density lipoprotein (HDL) to apolipoprotein B-containing lipoproteins as low-density lipoprotein (LDL) and very low-density particles (VLDL) [169]. In addition, mice also have bile acid compositions that differ from humans [168,170], affecting the enterohepatic cycle of cholesterol [170]. Several models for the disruption of lipid metabolism exist e.g., including LDL receptor (LDLR) −/− , apolipoprotein E (ApoE) −/− , LDLR and ApoE double knockout, ApoE3 Leiden transgenic mice and proprotein convertase subtilisin/kexin type 9 (PCSK9) gain of function models (Figure 4).…”

Pistachio Consumption Alleviates Inflammation and Improves Gut Microbiota Composition in Mice Fed a High-Fat Diet

“…Nevertheless, no study has characterized the links between pistachio supplementation, adiposity-related inflammation, and gut microbiota alterations. High-fat diet (HFD) mice are considered a good obese model to characterize the beneficial potential of various treatments on obesity-related disorders since they develop dyslipidemia, hyperglycemia [28,29], type 2 diabetes mellitus [30], hepatic steatosis [31], atherosclerosis [32], and neurodegeneration [33].…”

Altered Tregs Differentiation and Impaired Autophagy Correlate to Atherosclerotic Disease

“…ApoE is a component of lipoproteins (LPs), a biochemical assembly whose primary purpose is to transport lipids, fat-soluble vitamins and cholesterol into the lymph system and then into the blood. Mice lacking ApoE show a significant increase in total plasma cholesterol compared to wild-type animals and display atherosclerotic plaque development (28). In ApoE-KO mice, the progression of atherosclerotic disease is accelerated by treatment with aldosterone, a hormone which regulates blood pressure and promotes vascular function (29,30).…”