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  • Review Article
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Apolipoprotein B-containing lipoproteins in atherogenesis

Nature Reviews Cardiology volume 22, pages 399–413 (2025)Cite this article

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Abstract

Apolipoprotein B (apoB) is the main structural protein of LDLs, triglyceride-rich lipoproteins and lipoprotein(a), and is crucial for their formation, metabolism and atherogenic properties. In this Review, we present insights into the role of apoB-containing lipoproteins in atherogenesis, with an emphasis on the mechanisms leading to plaque initiation and growth. LDL, the most abundant cholesterol-rich lipoprotein in plasma, is causally linked to atherosclerosis. LDL enters the artery wall by transcytosis and, in vulnerable regions, is retained in the subendothelial space by binding to proteoglycans via specific sites on apoB. A maladaptive response ensues. This response involves modification of LDL particles, which promotes LDL retention and the release of bioactive lipid products that trigger inflammatory responses in vascular cells, as well as adaptive immune responses. Resident and recruited macrophages take up modified LDL, leading to foam cell formation and ultimately cell death due to inadequate cellular lipid handling. Accumulation of dead cells and cholesterol crystallization are hallmarks of the necrotic core of atherosclerotic plaques. Other apoB-containing lipoproteins, although less abundant, have substantially greater atherogenicity per particle than LDL. These lipoproteins probably contribute to atherogenesis in a similar way to LDL but might also induce additional pathogenic mechanisms. Several targets for intervention to reduce the rate of atherosclerotic lesion initiation and progression have now been identified, including lowering plasma lipoprotein levels and modulating the maladaptive responses in the artery wall.

Key points

  • LDL is the main carrier of cholesterol in the blood and of circulating cholesterol into the artery wall.

  • LDL is a proven causative factor for atherosclerotic cardiovascular disease, and reducing the plasma levels of LDL substantially reduces cardiovascular risk.

  • Subendothelial retention of LDL and other apolipoprotein B-containing lipoproteins is the primary trigger for the development of atherosclerosis.

  • Retained LDL becomes modified in the artery wall, and the focal accumulation of modified lipoproteins triggers the recruitment of monocytes and macrophages.

  • Damage-associated molecular patterns, formed when retained LDL is modified, induce a maladaptive immune response.

  • Different species of apolipoprotein B-containing lipoproteins are not equally atherogenic; triglyceride-rich lipoproteins and their remnants and lipoprotein(a) are markedly more atherogenic than LDL.

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Fig. 1: Early stages of atherogenesis.
Fig. 2: Cellular responses to LDL retention.
Fig. 3: Concepts in atherogenicity of apoB-containing lipoproteins.

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Authors and Affiliations

  1. Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden

    Jan Borén

  2. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK

    Chris J. Packard

  3. Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria

    Christoph J. Binder

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  1. Jan Borén
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  2. Chris J. Packard
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  3. Christoph J. Binder
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Correspondence to Jan Borén.

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Borén, J., Packard, C.J. & Binder, C.J. Apolipoprotein B-containing lipoproteins in atherogenesis. Nat Rev Cardiol 22, 399–413 (2025). https://doi.org/10.1038/s41569-024-01111-0

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