eprintid: 226114 rev_number: 22 eprint_status: archive userid: 29814 dir: disk0/00/22/61/14 datestamp: 2020-11-12 11:17:56 lastmod: 2025-06-11 08:31:53 status_changed: 2020-11-12 11:17:56 type: article metadata_visibility: show creators_name: Beazer, Jack David creators_name: Patanapirunhakit, Patamat creators_name: Gill, Jason M.R. creators_name: Graham, Delyth creators_name: Karlsson, Helen creators_name: Ljunggren, Stefan creators_name: Mulder, Monique creators_name: Freeman, Dilys J. creators_orcid: 0000-0001-6978-3072 creators_orcid: 0000-0003-3615-0986 creators_orcid: 0000-0002-7328-4708 creators_orcid: 0000-0002-6078-5271 title: High-density lipoprotein’s vascular protective functions in metabolic and cardiovascular disease - could extracellular vesicles be at play? ispublished: pub divisions: 25200000 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. date: 2020-11-19 date_type: published publisher: Portland Press id_number: 10.1042/CS20200892 copyright_holders: Copyright © 2020 The Author(s). prior: First published in Clinical Science 134(22):2977-2986 repro: Reproduced in accordance with the publisher copyright policy uniqueid: glaseprints:2020-226114 issn_online: 1470-8736 funding_project_code: 305659 funding_project_name: BHF 4-Year PhD Studentship Award 2018 funding_investigator_name: Rhian Touyz funding_funder_name: British Heart Foundation (BHF) funding_funder_code: FS/18/58/34179 funding_investigator_dept: CAMS - Cardiovascular Science pubmed_id: 33210708 euro_pubmed_id: 33210708 full_text_status: public publication: Clinical Science volume: 134 number: 22 pagerange: 2977-2986 refereed: TRUE issn: 0143-5221 oa_research_materials_ack: No hoa_compliant: 511 hoa_emb_len: 12 hoa_ref_pan: AB hoa_date_acc: 2020-11-09 hoa_date_pub: 2020-11-19 hoa_date_fcd: 2020-11-12 hoa_date_foa: 2021-11-24 hoa_version_fcd: AM hoa_exclude: FALSE hoa_gold: FALSE rioxx2_apc_input: not required citation: Beazer, Jack David , Patanapirunhakit, Patamat , Gill, Jason M.R. , Graham, Delyth , Karlsson, Helen, Ljunggren, Stefan, Mulder, Monique and Freeman, Dilys 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) document_url: https://eprints.gla.ac.uk/226114/2/226114.pdf