Atherosclerosis Mechanisms and Animal Models

Atherosclerosis is a chronic, progressive disease characterised by lipid accumulation, inflammation and fibrous cap formation within the arterial wall. Endothelial dysfunction initiates the process by permitting modified lipoproteins, notably oxidised low-density lipoprotein (ox-LDL), to infiltrate the intima. Recruited monocytes differentiate into macrophages and internalise ox-LDL, forming foam cells that aggregate into fatty streaks. Subsequent smooth muscle cell migration and extracellular matrix deposition advance plaque complexity. Plaque instability, driven by ongoing inflammation, matrix degradation and neovascularisation, can culminate in rupture and thrombosis, leading to myocardial infarction or stroke. Animal models have been indispensable for dissecting these stages. Genetically modified mice, including apolipoprotein E-deficient and LDL receptor-deficient strains, recapitulate hyperlipidaemia and spontaneous lesion development within weeks. Larger models, such as cholesterol-fed rabbits and pigs, better mirror human lipoprotein profiles and plaque morphology. Emerging systems, including zebrafish and non-human primates, offer complementary insights into vascular biology, immunometabolism and therapeutic interventions. Together, these models underpin mechanistic discovery, preclinical evaluation of lipid-lowering and anti-inflammatory agents, and the translation of imaging biomarkers for early detection and risk stratification.

Research from Nature Portfolio

Recent studies have harnessed plasma metabolomics in apolipoprotein E-deficient mice to map stage-specific biochemical alterations during atherosclerotic progression. Comprehensive profiling revealed early perturbations in sphingomyelin and cytidine diphosphate–diacylglycerol pathways preceding overt lesion formation. As plaques advanced, distinct elevations in phosphatidylethanolamine and glycosphingolipid metabolites were observed, delineating metabolic signatures of lesion severity. This metabolomic framework not only uncovers previously unrecognised lipid circuits implicated in vascular inflammation and smooth muscle cell dysfunction but also highlights candidate biomarkers for non-invasive staging of atherogenesis and assessment of therapeutic efficacy.

Atherosclerosis Mechanisms and Animal Models publication trend

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

Technical terms

Endothelial dysfunction: Impairment of the arterial lining that increases permeability and pro-inflammatory signalling.

Oxidised LDL: Low-density lipoprotein modified by oxidative reactions, central to foam cell formation.

Foam cell: Lipid-laden macrophage within the arterial intima contributing to plaque growth.

ApoE-deficient mouse: Genetically engineered mouse lacking apolipoprotein E, used to model hyperlipidaemia and atherogenesis.

Metabolomics: Systematic analysis of small-molecule metabolites to characterise dynamic biochemical changes.

Sphingolipid metabolism: Pathways governing ceramide and sphingomyelin synthesis, influencing cell signalling and vascular inflammation.

References

1. Itaconate suppresses atherosclerosis by activating a Nrf2-dependent anti-inflammatory response in macrophages in mice. Journal of Clinical Investigation (2023).
2. Dysregulation of Ceramide Metabolism Is Linked to Iron Deposition and Activation of Related Pathways in the Aorta of Atherosclerotic Miniature Pigs. Antioxidants (2023).
3. Comprehensive Plasma Metabolomic Analyses of Atherosclerotic Progression Reveal Alterations in Glycerophospholipid and Sphingolipid Metabolism in Apolipoprotein E-deficient Mice. Scientific Reports (2016).