HDL remodeling during the acute phase response.

HDL remodeling during the acute phase response.
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DOI:
10.1161/atvbaha.108.178681
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发表时间:
2009-02
期刊:
Arteriosclerosis, thrombosis, and vascular biology
影响因子:
--
通讯作者:
de Beer FC
de Beer FC
中科院分区:
其他
文献类型:
--
作者:
Jahangiri A;de Beer MC;Noffsinger V;Tannock LR;Ramaiah C;Webb NR;van der Westhuyzen DR;de Beer FC

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研究血清淀粉样蛋白A(SAA)、Ⅱ A型分泌型磷脂酶A2(sPLA 2-IIA)和胆固醇酯转运蛋白(CETP)在心脏手术后急性期(AP)反应中对HDL重构和胆固醇流出的相互作用。在心脏手术前(AP前)、心脏手术后24小时(AP- 1d)和心脏手术后5天(AP- 5d)采集患者的血浆。在AP- 1d样品中SAA水平增加了16倍。sPLA 2-IIA活性从AP前的77.7 ± 38.3 U/ml增加到AP- 1d的281.4 ± 57.1 U/ml(p < 0.001)。CETP质量和活性的降低与HDL胆固醇水平的降低相称。SAA、sPLA 2-IIA和CETP在体外的联合作用显著重塑HDL,从AP前和AP- 1d HDL产生贫脂apoA-I。这种重塑的净结果是在急性期反应期间ABCA 1和ABCG 1依赖性胆固醇流出的相对保留。我们的结果表明,急性期反应期间血浆蛋白的许多复杂变化显着重塑了HDL,并具有功能影响,特别是胆固醇流出能力的相对保留。
To study the interactive action of serum amyloid A (SAA), group IIA secretory phospholipase A2 (sPLA2-IIA) and cholesteryl ester transfer protein (CETP) on HDL remodeling and cholesterol efflux during the acute phase (AP) response elicited in humans following cardiac surgery. Plasma was collected from patients prior to (pre-AP), 24 hours after (AP- 1d) and 5 days after cardiac surgery (AP- 5d). SAA levels were increased 16-fold in AP- 1d samples. The activity of sPLA2-IIA was increased from 77.7 ± 38.3 U/ml (pre-AP) to 281.4 ± 57.1 U/ml (AP- 1d; p < 0.001). CETP mass and activity reduction was commensurate to the reduction of HDL cholesterol levels. The combined action of SAA, sPLA2-IIA and CETP in vitro markedly remodeled HDL with the generation of lipid-poor apoA-I from both pre-AP and AP- 1d HDL. The net result of this remodeling was a relative preservation of ABCA1 and ABCG1-dependent cholesterol efflux during the acute phase response. Our results show that the many and complex changes in plasma proteins during the acute phase response markedly remodel HDL with functional implications, particularly the relative retention of cholesterol efflux capacity.