Anti-inflammatory effects of apolipoprotein A-I in the rabbit.
OBJECTIVE
Infusions of apoA-I in the lipid-free form or as a constituent of discoidal reconstituted high-density lipoproteins, (A-I)rHDL, markedly inhibit acute vascular inflammation in normocholesterolemic New Zealand White (NZW) rabbits. This effect is apparent even when apoA-I is administered 24h prior to the inflammatory insult. The present study asks if this benefit is related to an improved anti-inflammatory capacity of the high-density lipoprotein (HDL) fraction, or to increased arterial expression of genes that inhibit inflammation.


RESULTS
The ability of apoA-I to increase the anti-inflammatory capacity of HDL was assessed by infusing normocholesterolemic NZW rabbits with saline, lipid-free apoA-I or (A-I)rHDL. The infused apoA-I incorporated rapidly into the rabbit HDL fraction. The animals were sacrificed at 5 or 360 min post-infusion and plasma was collected. HDL were isolated by ultracentrifugation and incubated with cytokine-activated cultured human coronary artery endothelial cells. HDL from animals sacrificed at 5 min post-apoA-I infusion had a slightly enhanced anti-inflammatory capacity relative to HDL from the saline-infused animals. The anti-inflammatory capacity of HDL from the animals sacrificed at 360 min post-apoA-I infusion was comparable to that of HDL from the saline-infused animals. The effect of (A-I)rHDL infusions on arterial 3β-hydroxysteroid-Δ24 reductase (DHCR24) and endothelial adhesion molecule expression was investigated in cholesterol-fed NZW rabbits. Relative to animals infused with saline, (A-I)rHDL infusions decreased aortic VCAM-1 and ICAM-1 protein expression by 73 and 54%, respectively (p<0.05), and increased DHCR24 mRNA levels by 56% (p<0.0001).


CONCLUSIONS
ApoA-I inhibits vascular inflammation in NZW rabbits, at least in part, by increasing DHCR24 expression.
Patel
Sanjay
S
Lipid Research Group, The Heart Research Institute, Sydney, NSW 2042, Australia.
Di Bartolo
Belinda A
BA
Nakhla
Shirley
S
Heather
Alison K
AK
Mitchell
Todd W
TW
Jessup
Wendy
W
Celermajer
David S
DS
Barter
Philip J
PJ
Rye
Kerry-Anne
KA
D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism*; D003331:Coronary Vessels / Q000166:cytology; D042783:Endothelial Cells / Q000166:cytology; D006801:Humans; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D044925:Oxidoreductases Acting on CH-CH Group Donors; C499055:DHCR24 protein, human