Table 8.

Examples of animal models that mimic human atherosclerosis

Species	Model	Main changes in the heart and vasculature	Animal-free alternatives	Refs
Pig	Familial hypercholesterolaemia	Atherosclerotic lesions of all vessels	Studies on certain aspects of atherosclerosis: Single-cell technologies human tissue samples152,154 2D and 3D in vitro models Refinement and reduction	138,139
	Yucatan and Sinclair miniature pigs fed with Alloxan resulting in diabetes	Human-like atherosclerotic lesions and microvascular diseases		140,141
	Ossabaw pigs	Obesity and metabolic syndrome like humans		142
	PCSK9 gain-of-function mutant	Hypertension, diabetes, kidney disease, endothelial dysfunction		143,144
Non-human primate	High-fat, high-cholesterol diet in Rhesus and cynomolgous macaques	Slow development of atherosclerosis		146
	Novel gene-modification technologies, e.g. CRISPR/Cas9	Accelerated atherosclerosis		146
Mouse	Transgenic mice with lack of genes involved in lipid metabolism (LDL-receptor, apolipoprotein E)	Accelerated atherosclerosis; spontaneous plaque rupture is rare		148,149
		Refinement: Induction of plaque rupture		150,151
	SRBI−/−/ApoE−/−, Fb1−/−ApoE−/−	Spontaneous plaque rupture with end-organ damage including stroke and MI		40,41