Abnormal High-Density Lipoprotein Induces Endothelial Dysfunction via Activation of Toll-like Receptor-2

被引：295

作者：

Speer, Thimoteus ^{[1
,2
,3
]}

Rohrer, Lucia ^{[5
,6
]}

Blyszczuk, Przemyslaw ^{[1
,2
]}

Shroff, Rukshana ^{[7
,8
]}

Kuschnerus, Kira ^{[1
,2
]}

Kraenkel, Nicolle ^{[1
,2
]}

Kania, Gabriela ^{[1
,2
]}

Zewinger, Stephen ^{[3
]}

Akhmedov, Alexander ^{[1
,2
]}

Shi, Yi ^{[1
,2
]}

Martin, Tina ^{[3
]}

Perisa, Damir ^{[6
]}

Winnik, Stephan ^{[1
,2
]}

Mueller, Maja F. ^{[1
,2
]}

Sester, Urban ^{[3
]}

Wernicke, Gabriel ^{[3
]}

Jung, Andreas ^{[3
]}

Gutteck, Ursula ^{[6
]}

Eriksson, Urs ^{[1
,9
]}

Geisel, Juergen ^{[4
]}

Deanfield, John

von Eckardstein, Arnold ^{[5
,6
]}

Luescher, Thomas F. ^{[1
,2
,5
]}

Fliser, Danilo ^{[3
]}

Bahlmann, Ferdinand H. ^{[3
]}

Landmesser, Ulf ^{[1
,2
]}

机构：

[1] Univ Zurich, Univ Zurich Hosp, Ctr Cardiovasc, CH-8091 Zurich, Switzerland

[2] Univ Zurich, Inst Physiol, CH-8091 Zurich, Switzerland

[3] Saarland Univ Hosp, Dept Internal Med Nephrol & Hypertens, D-66421 Homburg, Germany

[4] Saarland Univ Hosp, Inst Clin Chem, D-66421 Homburg, Germany

[5] Univ Zurich, Ctr Integrat Human Physiol, CH-8091 Zurich, Switzerland

[6] Univ Zurich Hosp, Inst Clin Chem, CH-8001 Zurich, Switzerland

[7] UCL, Inst Child Hlth, Vasc Physiol Unit, London WC1N 3JE, England

[8] Great Ormond St Hosp Sick Children, Renal Unit, London WC1N 3JH, England

[9] GZO Spital Wetzikon, Dept Internal Med, CH-8620 Wetzikon, Switzerland

来源：

IMMUNITY | 2013年 / 38卷 / 04期

基金：

瑞士国家科学基金会;

关键词：

CHRONIC KIDNEY-DISEASE; NITRIC-OXIDE SYNTHASE; STAGE RENAL-DISEASE; ASYMMETRIC DIMETHYLARGININE; SCAVENGER RECEPTOR; OXIDATIVE STRESS; PROGENITOR CELLS; BLOOD-PRESSURE; HEART-DISEASE; ATHEROSCLEROSIS;

D O I：

10.1016/j.immuni.2013.02.009

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Endothelial injury and dysfunction (ED) represent a link between cardiovascular risk factors promoting hypertension and atherosclerosis, the leading cause of death in Western populations. High-density lipoprotein (HDL) is considered antiatherogenic and known to prevent ED. Using HDL from children and adults with chronic kidney dysfunction (HDLCKD), a population with high cardiovascular risk, we have demonstrated that HDLCKD incontrast toHDL(Healthy) promoted endothelial superoxide production, substantially reduced nitric oxide (NO) bioavailability, and subsequently increased arterial blood pressure (ABP). We have identified symmetric dimethylarginine (SDMA) in HDLCKD that causes transformation from physiological HDL into an abnormal lipoprotein inducing ED. Furthermore, we report that HDLCKD reduced endothelial NO availability via toll-like receptor-2 (TLR-2), leading to impaired endothelial repair, increased proinflammatory activation, and ABP. These data demonstrate how SDMA can modify the HDL particle to mimic a damage-associated molecular pattern that activates TLR-2 via a TLR-1- or TLR-6-coreceptor-independent pathway, linking abnormal HDL to innate immunity, ED, and hypertension.

引用

页码：754 / 768

页数：15

共 60 条

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