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Immunity. 2013 Apr 18;38(4):754-68. doi: 10.1016/j.immuni.2013.02.009. Epub 2013 Mar 7.

Abnormal high-density lipoprotein induces endothelial dysfunction via activation of Toll-like receptor-2.

Author information

1
Cardiovascular Center, Cardiology, University Hospital Zurich and Cardiovascular Research, Institute of Physiology, University of Zurich, Zurich, Switzerland. timo.speer@uks.eu

Abstract

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 (HDL(CKD)), a population with high cardiovascular risk, we have demonstrated that HDL(CKD) in contrast to HDL(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 HDL(CKD) that causes transformation from physiological HDL into an abnormal lipoprotein inducing ED. Furthermore, we report that HDL(CKD) 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.

PMID:
23477738
DOI:
10.1016/j.immuni.2013.02.009
[Indexed for MEDLINE]
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