Inflammation modulates human HDL composition and function in vivo

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• 作者：Margarita de la Llera Moya^a ; ¹ ; Fiona C. McGillicuddy^b ; ^c ; ^d ; ¹ ; Christine C. Hinkle^b ; ^c ; Michael Byrne^b ; ^c ; Michelle R. Joshi^a ; Vihn Nguyen^a ; Jennifer Tabita-Martinez^b ; ^c ; Megan L. Wolfe^b ; ^c ; Karen Badellino^b ; ^c ; Leticia Pruscino^b ; ^c ; Nehal N. Mehta^b ; ^c ; Bela F. Asztalos^e ; Muredach P. Reilly^b ; ^c ; ^{muredach@mail.med.upenn.edu}
• 关键词：Inflammation ; Atherosclerosis ; Cholesterol ; Lipoproteins ; Macrophages
• 刊名：Atherosclerosis
• 出版年：2012
• 期刊代码：28_00219150
• 类别：med
• 出版时间：June, 2012
• 卷：222
• 期：2
• 页码：390-394
• 文件大小：544 K

摘要

Objectives

Inflammation may directly impair HDL functions, in particular reverse cholesterol transport (RCT), but limited data support this concept in humans.

Methods and results

We employed low-dose human endotoxemia to assess the effects of inflammation on HDL and RCT-related parameters in vivo. Endotoxemia induced remodelling of HDL with depletion of pre-尾1a HDL particles determined by 2-D gel electrophoresis (鈭?2.2 卤 9.3%at 24 h, p < 0.05) as well as small (鈭?3.0 卤 5.1%, p < 0.01, at 24 h) and medium (鈭?7.6 卤 8.0%at 16 h, p < 0.001) HDL estimated by nuclear magnetic resonance (NMR). This was associated with induction of class II secretory phospholipase A2 (鈭?6 fold increase) and suppression of lecithin:cholesterol acyltransferase activity (鈭?0.8 卤 3.4%at 24 h, p < 0.01) and cholesterol ester transfer protein mass (鈭?2.2 卤 6.8%at 24 h, p < 0.001). The HDL fraction, isolated following endotoxemia, had reduced capacity to efflux cholesterol in vitro from SR-BI and ABCA1, but not ABCG1 transporter cell models.

Conclusions

These data support the concept that 鈥渁therogenic-HDL dysfunction鈥?and impaired RCT occur in human inflammatory syndromes, largely independent of changes in plasma HDL-C and ApoA-I levels.