High-density lipoprotein revisited: biological functions and clinical relevance

Author:

von Eckardstein Arnold1ORCID,Nordestgaard Børge G234ORCID,Remaley Alan T5ORCID,Catapano Alberico L67ORCID

Affiliation:

1. Institute of Clinical Chemistry, University Hospital Zurich and University of Zurich , Zurich , Switzerland

2. Department of Clinical Biochemistry, Copenhagen University Hospital, Herlev and Gentofte Hospital , Herlev , Denmark

3. The Copenhagen General Population Study, Copenhagen University Hospital, Herlev and Gentofte Hospital , Herlev , Denmark

4. Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen , Denmark

5. Lipoprotein Metabolism Section, Translational Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, MD , USA

6. Department of Pharmacological and Biomolecular Sciences, University of Milan , Milan , Italy

7. IRCCS MultiMedica, Sesto S. Giovanni , Milan , Italy

Abstract

Abstract Previous interest in high-density lipoproteins (HDLs) focused on their possible protective role in atherosclerotic cardiovascular disease (ASCVD). Evidence from genetic studies and randomized trials, however, questioned that the inverse association of HDL-cholesterol (HDL-C) is causal. This review aims to provide an update on the role of HDL in health and disease, also beyond ASCVD. Through evolution from invertebrates, HDLs are the principal lipoproteins, while apolipoprotein B-containing lipoproteins first developed in vertebrates. HDLs transport cholesterol and other lipids between different cells like a reusable ferry, but serve many other functions including communication with cells and the inactivation of biohazards like bacterial lipopolysaccharides. These functions are exerted by entire HDL particles or distinct proteins or lipids carried by HDL rather than by its cholesterol cargo measured as HDL-C. Neither does HDL-C measurement reflect the efficiency of reverse cholesterol transport. Recent studies indicate that functional measures of HDL, notably cholesterol efflux capacity, numbers of HDL particles, or distinct HDL proteins are better predictors of ASCVD events than HDL-C. Low HDL-C levels are related observationally, but also genetically, to increased risks of infectious diseases, death during sepsis, diabetes mellitus, and chronic kidney disease. Additional, but only observational, data indicate associations of low HDL-C with various autoimmune diseases, and cancers, as well as all-cause mortality. Conversely, extremely high HDL-C levels are associated with an increased risk of age-related macular degeneration (also genetically), infectious disease, and all-cause mortality. HDL encompasses dynamic multimolecular and multifunctional lipoproteins that likely emerged during evolution to serve several physiological roles and prevent or heal pathologies beyond ASCVD. For any clinical exploitation of HDL, the indirect marker HDL-C must be replaced by direct biomarkers reflecting the causal role of HDL in the respective disease.

Funder

Swiss National Science Foundation

Herlev and Gentofte Hospital

Copenhagen University Hospital

Italian Ministry of Health

Publisher

Oxford University Press (OUP)

Subject

Cardiology and Cardiovascular Medicine

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