Table 1:
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-oxidative58–60 | Inversely with presence of ASCVD or diabetes58–60 |
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