High-density lipoprotein’s vascular protective functions in metabolic and cardiovascular disease - could extracellular vesicles be at play?

Beazer, J. D. , Patanapirunhakit, P., Gill, J. M.R. , Graham, D. , Karlsson, H., Ljunggren, S., Mulder, M. and Freeman, D. J. (2020) High-density lipoprotein’s vascular protective functions in metabolic and cardiovascular disease - could extracellular vesicles be at play? Clinical Science, 134(22), pp. 2977-2986. (doi: 10.1042/CS20200892) (PMID:33210708)

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Abstract

High-density lipoprotein (HDL) is a circulating complex of lipids and proteins known primarily for its role in reverse cholesterol transport and consequent protection from atheroma. In spite of this, therapies aimed at increasing HDL concentration do not reduce the risk of cardiovascular disease (CVD), and as such focus has shifted towards other HDL functions protective of vascular health – including vasodilatory, anti-inflammatory, antioxidant and anti-thrombotic actions. It has been demonstrated that in disease states such as CVD and conditions of insulin resistance such as Type 2 diabetes mellitus (T2DM), HDL function is impaired owing to changes in the abundance and function of HDL-associated lipids and proteins, resulting in reduced vascular protection. However, the gold standard density ultracentrifugation technique used in the isolation of HDL also co-isolates extracellular vesicles (EVs). EVs are ubiquitous cell-derived particles with lipid bilayers that carry a number of lipids, proteins and DNA/RNA/miRNAs involved in cell-to-cell communication. EVs transfer their bioactive load through interaction with cell surface receptors, membrane fusion and endocytic pathways, and have been implicated in both cardiovascular and metabolic diseases – both as protective and pathogenic mediators. Given that studies using density ultracentrifugation to isolate HDL also co-isolate EVs, biological effects attributed to HDL may be confounded by EVs. We hypothesise that some of HDL’s vascular protective functions in cardiovascular and metabolic disease may be mediated by EVs. Elucidating the contribution of EVs to HDL functions will provide better understanding of vascular protection and function in conditions of insulin resistance and potentially provide novel therapeutic targets for such diseases.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Gill, Professor Jason and Graham, Dr Delyth and Freeman, Dr Dilys and Patanapirunhakit, Patamat and Beazer, Jack David
Authors: Beazer, J. D., Patanapirunhakit, P., Gill, J. M.R., Graham, D., Karlsson, H., Ljunggren, S., Mulder, M., and Freeman, D. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Clinical Science
Publisher:Portland Press
ISSN:0143-5221
ISSN (Online):1470-8736
Copyright Holders:Copyright © 2020 The Author(s).
First Published:First published in Clinical Science 134(22):2977-2986
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
305659BHF 4-Year PhD Studentship Award 2018Rhian TouyzBritish Heart Foundation (BHF)FS/18/58/34179CAMS - Cardiovascular Science