Acute hypertriglyceridaemia in humans increases the triglyceride content and decreases the anti-inflammatory capacity of high density lipoproteins.
BACKGROUND
Post-prandial hypertriglyceridaemia is a risk factor for cardiovascular disease, although the underlying mechanisms remain unclear. High density lipoproteins (HDL) have been shown to be atheroprotective, in part through attenuation of vascular inflammation. In this study, the influence of acute hypertriglyceridaemia on the composition and anti-inflammatory properties of HDL was investigated.


METHODS
Eight fasting healthy male subjects (34+/-2 years) received 20% Intralipid (15 mg/kg/h) or saline, on separate occasions in random order. At baseline and 60 min post-infusion, the total HDL fraction was isolated and its chemical composition determined. HDL were added to TNF-alpha stimulated human coronary artery endothelial cells and VCAM-1 and ICAM-1 expression was determined by flow cytometry.


RESULTS
Serum triglyceride (97.4+/-8.5mg/dL baseline, 283.2+/-35.4 mg/dL post-infusion, p<0.001) and HDL triglyceride content (3.8+/-0.5% HDL mass baseline, 5.3+/-0.9% HDL mass post-infusion, p<0.05) increased significantly after Intralipid infusion. HDL post-Intralipid were significantly less anti-inflammatory compared with control (e.g. at 8 microM apoA-I, %VCAM-1 expression 54+/-5 post-saline, 73+/-4 post-Intralipid, p=0.01; %ICAM-1 expression 94+/-1 post-saline, 99.4+/-0.6 post-Intralipid, p<0.01). There was also a significant correlation between HDL triglyceride content and VCAM-1 expression (R=0.70, p=0.005); as well as between plasma triglyceride levels and both VCAM-1 (R=0.71, p<0.005) and ICAM-1 expression (R=0.80, p<0.005).


CONCLUSIONS
Acute hypertriglyceridaemia, simulating the post-prandial state, results in triglyceride-rich HDL with impaired anti-inflammatory capacity.
Patel
Sanjay
S
The Heart Research Institute, Sydney, Australia. sanjay.patel@bigpond.com
Puranik
Rajesh
R
Nakhla
Shirley
S
Lundman
Pia
P
Stocker
Roland
R
Wang
Xiao S
XS
Lambert
Gilles
G
Rye
Kerry-Ann
KA
Barter
Philip J
PJ
Nicholls
Stephen J
SJ
Celermajer
David S
DS
D000208:Acute Disease; D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood* / Q000276:immunology; D007249:Inflammation / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000097:blood; D007262:Infusions, Intravenous; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D019518:Postprandial Period; D011897:Random Allocation; D014280:Triglycerides / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D005217:Fat Emulsions, Intravenous; C034396:HDL-triglyceride; D018836:Inflammation Mediators; D008075:Lipoproteins, HDL; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1