Pathophysiology of Atherosclerosis and Lipoprotein Interactions

Atherosclerosis is a progressive condition marked by the accumulation of lipid-rich plaques within the arterial intima, where interactions between circulating lipoproteins and the vessel wall initiate and drive disease progression. ApoB-containing lipoproteins, notably low-density lipoprotein (LDL), penetrate the endothelium and become trapped by negatively charged proteoglycans. Within the intimal microenvironment, these retained particles undergo oxidative, enzymatic or pH-mediated modifications, leading to aggregation, fusion and enhanced retention. Modified LDL is avidly taken up by macrophages via scavenger receptors, forming foam cells and perpetuating local inflammation. Endothelial dysfunction, inflammatory cytokine release and impaired cholesterol efflux by high-density lipoprotein (HDL) further destabilise plaques. Advances have elucidated molecular mechanisms of lipoprotein modification, the role of extracellular matrix components and processes of macrophage polarisation. These insights point to novel therapeutic strategies aimed at preventing lipoprotein retention, modulating enzymatic activity and restoring cholesterol balance to stabilise or regress plaques, with broad implications for reducing global cardiovascular morbidity and mortality.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Pathophysiology of Atherosclerosis and Lipoprotein Interactions publication trend

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

Technical terms

Atherosclerosis: Chronic arterial disease characterised by plaque accumulation in the intima.

Lipoproteins (LDL, HDL): Circulating complexes that transport cholesterol and triglycerides.

Foam cells: Macrophages engorged with modified lipids within plaques.

Proteoglycans: Extracellular matrix proteins with glycosaminoglycan chains that retain lipoproteins.

Sphingomyelinase: Enzyme that hydrolyses sphingomyelin in LDL, promoting particle aggregation.

References

1. Recombinant human proteoglycan 4 lowers inflammation and atherosclerosis susceptibility in female low‐density lipoprotein receptor knockout mice. The Journal of Physiology (2024).
2. Effect of Sphingomyelinase-Treated LDLs on HUVECs. Molecules (2023).
3. Acidification of the intimal fluid: the perfect storm for atherogenesis. Journal of Lipid Research (2014).
4. Aggregation, fusion, and vesicle formation of modified low density lipoprotein particles: molecular mechanisms and effects on matrix interactions. Journal of Lipid Research (2000).