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. Author manuscript; available in PMC: 2022 Jun 8.
Published in final edited form as: Circulation. 2021 Jun 7;143(23):2293–2309. doi: 10.1161/CIRCULATIONAHA.120.044221

Table 1:

Examples of HDL-associated proteins, lipids, and miRNAs associated with the presence or incidence of diseases or mortality

Molecules Function in HDL Disease association
Particles
HDL particle number Determines CEC45 Inversely with risk of ASCVD46
Small HDL Determines CEC45 Positively with diabetes, Inversely with risk of ASCVD45,47
Large HDL Determines CEC45 Positively with diabetes45, 47
 Prebeta-HDL HDL-precursor, determines CEC Positively with the presence of ASCVD48

Proteins
ApoA-I Structural component Activator of LCAT Ligand of HDL receptor and ABCA1 Anti-oxidative Total apoA-I: Inversely with incident ASCVD or mortality39, various posttranslational modifications of apoA-I are positively associated with presence of ASCVD42, 44
apoC-III Promotes apoptosis of endothelial cells and activation, inhibits cholesterol efflux49, 50 Positively with incident ASCVD or diabetes39, 51
apoE Hepatic Removal of HDL,52 stimulation of cholesterol efflux anti-inflammatory activities Inversely with risk of ASCVD and dementia1
Serum amyloid A Acute phase reactant inhibits cholesterol efflux and eNOS activation53 Positively with presence of ASCVD and mortality of patients with ASCVD or ESRD53, 54
Paraoxonase 1 Inhibition of lipid-peroxidation Inversely with presence of ASCVD or diabetes55
Pulmonary surfactant protein B Component of lung surfactant Positively with mortality in patients with ESRD or heart failure54, 56

Lipids

Cholesteryl esters Core lipid determining size and shape Inversely with presence and incidence of ASCVD, diabetes, and other diseases1
Triglycerides Core lipid Positively with mortality in ASCVD patients57
Phosphatidylcholines Determine fluidity of HDL and thereby cholesterol efflux capacity;45, 58 substrate for the generation of lyso-phospholipids Heterogeneous, depending on species45, 58
PC- and PE-plasmalogens Anti-oxidative5860 Inversely with presence of ASCVD or diabetes5860
Lysophosphatidylcholines (e.g. LPC18:1, LPC18:2) Enzymatically produced from HDL-derived lipids. Signalling Inversely with diabetes45, 61
sphingomyelins Determine rigidity of HDL and thereby cholesterol efflux capacity and anti-apoptotic activity towards endothelial cells;45 substrate for the generation of S1P and ceramides Some species inversely with presence of diabetes or ASCVD45, 61, 62
Sphingosine-1 phosphate Agonist of five G-protein coupled S1P receptors; Multiple vasoprotective,
anti-diabetic and anti-inflammatory actions63, 64
Inversely with presence of ASCVD or diabetes64

microRNAs

miR-223 Most abundant miRNA in HDL. Regulates VCAM expression in endothelial cells and cholesterol metabolism in liver65 Increased in ACS and diabetes. Decreases upon weight loss66, 67
miR-375-3p Secreted by pancreatic beta cells to HDL68 Increased levels in beta cell failure after islet transplantation69

HDL=high density lipoprotein; CEC=cholesterol efflux capacity; ASCVD=atherosclerotic cardiovascular disease; ApoA-I=apolipoprotein A-I; LCAT=lecithin–cholesterol acyltransferase; ABCA1=ATP-binding cassette transporter ABCA1; apoC-III=apolipoprotein C-III; apoE=apolipoprotein E; eNOS=endothelial nitric oxide synthase; ESRD=end-stage renaldisease; PC=phosphatidylcholine; PE=phosphatidylethanolamine; LPC= lysophosphatidylcholines; S1P=sphingosine-1-phosphate; miR=micro ribonucleic acid; VCAM=vascular cell adhesion molecule; ACS=acute coronary syndrome