Reconstituted high-density lipoprotein increases plasma high-density lipoprotein anti-inflammatory properties and cholesterol efflux capacity in patients with type 2 diabetes.
OBJECTIVE
Our aim was to investigate the effects of reconstituted high-density lipoprotein (rHDL) infusions on plasma high-density lipoprotein (HDL) anti-inflammatory properties and ex vivo cholesterol efflux in patients with type 2 diabetes.


BACKGROUND
The anti-inflammatory effects of HDL contribute to protection from cardiovascular events. Individuals with type 2 diabetes are at elevated risk for cardiovascular disease, and typically have low HDL with reduced anti-inflammatory properties.


METHODS
Thirteen fasting male patients (mean age 52 years) with type 2 diabetes mellitus received both rHDL (80 mg/kg of apolipoprotein A-I) and a saline placebo on separate occasions in a randomized cross-over design study. Changes in the ability of isolated HDL to influence the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in human coronary artery endothelial cells was the main outcome measure. Other outcome measures included expression of the key integrin, CD11b on patient monocytes, adhesiveness of patient neutrophils to fibrinogen, and the ability of plasma to promote cholesterol efflux to THP-1 macrophages.


RESULTS
Four and 72 h post-rHDL infusion, the anti-inflammatory properties of isolated HDL increased in parallel to their concentration in plasma (by up to 25%, p < 0.01). Participants' peripheral blood monocyte CD11b expression and neutrophil adhesion to a fibrinogen matrix was also reduced 72 h post-rHDL, compared with that seen in placebo (p = 0.02). rHDL increased the capacity of plasma to receive cholesterol from THP-1 macrophages by 1 h up to 72 h post-infusion (by 40% to 60%, p < 0.05).


CONCLUSIONS
rHDL infusions have significant, potentially atheroprotective effects in individuals with diabetes, including suppression of inflammation and enhancement of cholesterol efflux.
Patel
Sanjay
S
Heart Research Institute, Sydney, Australia.
Drew
Brian G
BG
Nakhla
Shirley
S
Duffy
Stephen J
SJ
Murphy
Andrew J
AJ
Barter
Phillip J
PJ
Rye
Kerry-Anne
KA
Chin-Dusting
Jaye
J
Hoang
Anh
A
Sviridov
Dmitri
D
Celermajer
David S
DS
Kingwell
Bronwyn A
BA
D039481:CD11b Antigen / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D007262:Infusions, Intravenous; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D008075:Lipoproteins, HDL / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D039481:CD11b Antigen; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1