Lipid Research Group, The Heart Research Institute, Sydney, New South Wales, Australia.
Arterioscler Thromb Vasc Biol. 2010 Apr;30(4):766-72. doi: 10.1161/ATVBAHA.109.201715. Epub 2010 Jan 28.
The goal of this study was to investigate the effects of nonenzymatic glycation on the antiinflammatory properties of apolipoprotein (apo) A-I.
Rabbits were infused with saline, lipid-free apoA-I from normal subjects (apoA-I(N)), lipid-free apoA-I nonenzymatically glycated by incubation with methylglyoxal (apoA-I(Glyc in vitro)), nonenzymatically glycated lipid-free apoA-I from subjects with diabetes (apoA-I(Glyc in vivo)), discoidal reconstituted high-density lipoproteins (rHDL) containing phosphatidylcholine and apoA-I(N), (A-I(N))rHDL, or apoA-I(Glyc in vitro), (A-I(Glyc in vitro))rHDL. At 24 hours postinfusion, acute vascular inflammation was induced by inserting a nonocclusive, periarterial carotid collar. The animals were euthanized 24 hours after the insertion of the collar. The collars caused intima/media neutrophil infiltration and increased endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). ApoA-I(N) infusion decreased neutrophil infiltration and VCAM-1 and ICAM-1 expression by 89%, 90%, and 66%, respectively. The apoA-I(Glyc in vitro) infusion decreased neutrophil infiltration by 53% but did not reduce VCAM-1 or ICAM-1 expression. ApoA-I(Glyc in vivo) did not inhibit neutrophil infiltration or adhesion molecule expression. (A-I(Glyc in vitro))rHDL also inhibited vascular inflammation less effectively than (A-I(N))rHDL. The reduced antiinflammatory properties of nonenzymatically glycated apoA-I were attributed to a reduced ability to inhibit nuclear factor-kappaB activation and reactive oxygen species formation.
Nonenzymatic glycation impairs the antiinflammatory properties of apoA-I.
本研究旨在探讨非酶糖基化对载脂蛋白（apo）A-I 抗炎特性的影响。
用生理盐水、正常受试者的无脂载脂蛋白 A-I（apoA-I（N））、用甲基乙二醛孵育非酶糖基化的无脂载脂蛋白 A-I（apoA-I（Glyc in vitro））、来自糖尿病患者的非酶糖基化无脂载脂蛋白 A-I（apoA-I（Glyc in vivo））、含磷脂酰胆碱和 apoA-I（N）的圆盘状重组高密度脂蛋白（rHDL）、（apoA-I（N））rHDL 或 apoA-I（Glyc in vitro）、（apoA-I（Glyc in vitro））rHDL 对兔子进行输注。输注后 24 小时，通过插入非闭塞性、血管旁颈动脉袖带诱导急性血管炎症。袖带插入后 24 小时处死动物。袖带引起内膜/中膜中性粒细胞浸润，并增加内皮细胞血管细胞黏附分子-1（VCAM-1）和细胞间黏附分子-1（ICAM-1）的表达。apoA-I（N）输注使中性粒细胞浸润分别减少 89%、90%和 66%，并使 VCAM-1 和 ICAM-1 的表达减少 90%、90%和 66%。apoA-I（Glyc in vitro）输注使中性粒细胞浸润减少 53%，但不减少 VCAM-1 或 ICAM-1 的表达。apoA-I（Glyc in vivo）不能抑制中性粒细胞浸润或黏附分子的表达。（apoA-I（Glyc in vitro））rHDL 抑制血管炎症的作用也不如（apoA-I（N））rHDL 有效。非酶糖基化的 apoA-I 抗炎特性降低归因于其抑制核因子-kappaB 激活和活性氧形成的能力降低。
非酶糖基化损害 apoA-I 的抗炎特性。
