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Review
. 2021 Jul 23;10(8):1869.
doi: 10.3390/cells10081869.

HDL in Atherosclerotic Cardiovascular Disease: In Search of a Role

Manuela Casula  1   2 , Ornella Colpani  1 , Sining Xie  1 , Alberico L Catapano  2   3 , Andrea Baragetti  2   3
Affiliations
Review

HDL in Atherosclerotic Cardiovascular Disease: In Search of a Role

Manuela Casula et al. Cells. .

Abstract

For a long time, high-density lipoprotein cholesterol (HDL-C) has been regarded as a cardiovascular disease (CVD) protective factor. Recently, several epidemiological studies, while confirming low plasma levels of HDL-C as an established predictive biomarker for atherosclerotic CVD, indicated that not only people at the lowest levels but also those with high HDL-C levels are at increased risk of cardiovascular (CV) mortality. This "U-shaped" association has further fueled the discussion on the pathophysiological role of HDL in CVD. In fact, genetic studies, Mendelian randomization approaches, and clinical trials have challenged the notion of HDL-C levels being causally linked to CVD protection, independent of the cholesterol content in low-density lipoproteins (LDL-C). These findings have prompted a reconsideration of the biological functions of HDL that can be summarized with the word "HDL functionality", a term that embraces the many reported biological activities beyond the so-called reverse cholesterol transport, to explain this lack of correlation between HDL levels and CVD. All these aspects are summarized and critically discussed in this review, in an attempt to provide a background scenario for the "HDL story", a lipoprotein still in search of a role.

Keywords: HDL cholesterol; HDL lipoproteins; genetics; pharmacological trials.

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Conflict of interest statement

Casula M., Colpani, O., Xie, S. and Baragetti A., report no disclosures. Catapano A.L., reports grants from Amgen, Sanofi, and Regeneron, and personal fees from Merck, Sanofi, Regeneron, AstraZeneca, Amgen, and Novartis, outside the submitted work.

Figures

Figure 1
Figure 1
Heterogeneity of the HDL class in atherosclerotic cardiovascular diseases. (A) HDL major types by form, diameters/density, or electrophoretic mobility, and their known association with risk of atherosclerotic cardiovascular disease (reporting increase in the risk from bottom to top). (B) Summary of unknown/uncertain associations between apolipoprotein content of HDL and risk of atherosclerotic cardiovascular disease (indicated by yellow question marks).
See this image and copyright information in PMC

References

    1. Camont L., Chapman M.J., Kontush A. Biological activities of HDL subpopulations and their relevance to cardiovascular disease. Trends Mol. Med. 2011;17:594–603. doi: 10.1016/j.molmed.2011.05.013. - DOI - PubMed
    1. Kostara C.E., Tsimihodimos V., Elisaf M.S., Bairaktari E.T. NMR-Based Lipid Profiling of High Density Lipoprotein Particles in Healthy Subjects with Low, Normal, and Elevated HDL-Cholesterol. J. Proteome Res. 2017;16:1605–1616. doi: 10.1021/acs.jproteome.6b00975. - DOI - PubMed
    1. Kontush A., Lindahl M., Lhomme M., Calabresi L., Chapman M.J., Davidson W.S. Structure of HDL: Particle subclasses and molecular components. Handb. Exp. Pharmacol. 2015;224:3–51. doi: 10.1007/978-3-319-09665-0_1. - DOI - PubMed
    1. Helgadottir A., Sulem P., Thorgeirsson G., Gretarsdottir S., Thorleifsson G., Jensson B.O., Arnadottir G.A., Olafsson I., Eyjolfsson G.I., Sigurdardottir O., et al. Rare SCARB1 mutations associate with high-density lipoprotein cholesterol but not with coronary artery disease. Eur. Heart J. 2018;39:2172–2178. doi: 10.1093/eurheartj/ehy169. - DOI - PMC - PubMed
    1. Zanoni P., Khetarpal S.A., Larach D.B., Hancock-Cerutti W.F., Millar J.S., Cuchel M., Der Ohannessian S., Kontush A., Surendran P., Saleheen D., et al. Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease. Science. 2016;351:1166–1171. doi: 10.1126/science.aad3517. - DOI - PMC - PubMed

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