Animal Models of Atherosclerosis Research

Atherosclerosis, the progressive accumulation of lipid-laden plaques within arterial walls, remains a leading cause of cardiovascular morbidity and mortality worldwide. Animal models have been indispensable for elucidating mechanisms of plaque initiation, progression and regression, as well as for preclinical evaluation of therapeutic and interventional strategies. Small rodents, particularly genetically engineered mice such as ApoE−/− and LDLR−/− strains, allow rapid investigation of hypercholesterolaemia and inflammatory pathways under tightly controlled dietary and genetic conditions. Larger models, including rabbits, pigs and primates, offer closer resemblance to human lipid metabolism, plaque architecture and vascular size, enabling studies of interventional devices and advanced imaging modalities. Emerging strategies include inducible genetic perturbations of lipid regulatory genes such as PCSK9, minimally invasive vascular injury techniques to mimic neointimal hyperplasia, and ex vivo perfusion of human tissues to bridge the translational gap. Lipidomic profiling across species has refined model selection by matching lipid fingerprints to human plasma. By spanning from fundamental mechanistic insights in rodents to translational human tissue platforms, the repertoire of animal and ex vivo models drives the development of novel diagnostics, pharmacotherapies and interventional procedures for atherosclerosis.

Research from Nature Portfolio

A novel ex vivo pump-perfused human limb platform maintains physiological perfusion of amputated tissue, permitting real-time intravascular imaging and molecular targeting of calcified plaques. This system replicates arterial haemodynamics for several hours and enables optical coherence tomography, intravascular ultrasound and fluorescence imaging of atherosclerotic lesions under clinical conditions. Complementary to this, comparative lipidomic profiling of multiple species has demonstrated that certain animal models, notably hamsters and pigs, share key plasma lipid species with humans. High-resolution mass spectrometry has identified conserved lipid signatures, informing the selection of species that best recapitulate human hyperlipidaemia and guiding translational study design in atherosclerosis research.

Animal Models of Atherosclerosis Research publication trend

The graph below shows the total number of articles in animal models of atherosclerosis research across all publications each year (not limited to Nature Index journals).

Technical terms

ApoE−/− mouse: A mouse genetically engineered to lack apolipoprotein E, leading to spontaneous hypercholesterolaemia and plaque formation.

PCSK9: Proprotein convertase subtilisin/kexin type 9, an enzyme that regulates LDL receptor levels and influences plasma cholesterol.

Neointimal hyperplasia: Thickening of the arterial intima due to smooth muscle cell proliferation and extracellular matrix deposition after vascular injury.

Ex vivo perfusion model: A system in which organs or tissues are maintained alive outside the body by circulating oxygenated blood or perfusate.

Lipidomic profiling: Comprehensive analysis of lipid species using high-resolution mass spectrometry to characterise lipid signatures.

References

1. Conventional Platinum Metal Implants Provoke Restenosis Responses in Atherogenic but Not Healthy Arteries. Sci (2023).
2. Incidence of microvascular dysfunction is increased in hyperlipidemic mice, reducing cerebral blood flow and impairing remote memory. Frontiers in Endocrinology (2024).
3. A novel translational model of atherosclerosis, the ex vivo pump-perfused amputated human limb model. Scientific Reports (2024).
4. A minimally invasive animal model of atherosclerosis and neointimal hyperplasia for translational research. European Radiology Experimental (2025).
5. Plasma lipidomic analysis reveals strong similarities between lipid fingerprints in human, hamster and mouse compared to other animal species. Scientific Reports (2018).