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  • Review Article
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Apolipoproteins in vascular biology and atherosclerotic disease

Nature Reviews Cardiology volume 19, pages 168–179 (2022)Cite this article

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Abstract

Apolipoproteins are important structural components of plasma lipoproteins that influence vascular biology and atherosclerotic disease pathophysiology by regulating lipoprotein metabolism. Clinically important apolipoproteins related to lipid metabolism and atherogenesis include apolipoprotein B-100, apolipoprotein B-48, apolipoprotein A-I, apolipoprotein C-II, apolipoprotein C-III, apolipoprotein E and apolipoprotein(a). Apolipoprotein B-100 is the major structural component of VLDL, IDL, LDL and lipoprotein(a). Apolipoprotein B-48 is a truncated isoform of apolipoprotein B-100 that forms the backbone of chylomicrons. Apolipoprotein A-I provides the scaffolding for lipidation of HDL and has an important role in reverse cholesterol transport. Apolipoproteins C-II, apolipoprotein C-III and apolipoprotein E are involved in triglyceride-rich lipoprotein metabolism. Apolipoprotein(a) covalently binds to apolipoprotein B-100 to form lipoprotein(a). In this Review, we discuss the mechanisms by which these apolipoproteins regulate lipoprotein metabolism and thereby influence vascular biology and atherosclerotic disease. Advances in the understanding of apolipoprotein biology and their translation into therapeutic agents to reduce the risk of cardiovascular disease are also highlighted.

Key points

  • Apolipoproteins are specialized proteins that regulate lipoprotein metabolism and influence normal human vascular biology and atherosclerotic cardiovascular disease.

  • Clinically important apolipoproteins include apolipoprotein B-100, apolipoprotein B-48, apolipoprotein A-I, apolipoprotein C-II, apolipoprotein C-III, apolipoprotein E and apolipoprotein(a).

  • Apolipoprotein B-100, apolipoprotein B-48 and apolipoprotein(a) form the structural backbone of atherogenic lipoproteins, including VLDL, IDL, LDL, chylomicrons and lipoprotein(a).

  • Apolipoprotein A-I regulates HDL metabolism and reverses cholesterol transport.

  • Apolipoprotein C-II, apolipoprotein C-III and apolipoprotein E regulate triglyceride-rich lipoprotein metabolism.

  • Therapeutic agents directly targeting apolipoproteins have been developed, and their effectiveness in reducing risk in populations of patients at high risk of atherosclerotic cardiovascular disease is being evaluated.

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Fig. 1: ApoB-100 in human health and atherosclerotic disease.
Fig. 2: ApoA-I and reverse cholesterol transport.
Fig. 3: Role of apoC-II and apoC-III in TRL metabolism.
Fig. 4: Atherogenic mechanisms of apo(a).

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  1. Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA

    Anurag Mehta

  2. Center for Prevention of Cardiovascular Disease, Section on Cardiovascular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Michael D. Shapiro

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M.D.S. has served on scientific advisory boards for Alexion, Amgen, Esperion and Novartis. A.M. declares no competing interests.

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Mehta, A., Shapiro, M.D. Apolipoproteins in vascular biology and atherosclerotic disease. Nat Rev Cardiol 19, 168–179 (2022). https://doi.org/10.1038/s41569-021-00613-5

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