Anti-inflammatory effects of apolipoprotein A-I in the rabbit

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• 作者：Sanjay Patel ; Belinda A. Di Bartolo ; Shirley Nakhla ; Alison K. Heather ; Todd W. Mitchell ; Wendy Jessup ; David S. Celermajer ; Philip J. Barter ; Kerry-Anne Rye
• 关键词：HDL ; apoA-I ; Inflammation ; VCAM-1 ; ICAM-1 ; DHCR24
• 刊名：Atherosclerosis
• 出版年：2010
• 出版时间：October 2010
• 年：2010
• 卷：212
• 期：2
• 页码：392-397
• 全文大小：539 K

文摘

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 24 h 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.

Methods and 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).

Conclusion

ApoA-I inhibits vascular inflammation in NZW rabbits, at least in part, by increasing DHCR24 expression.