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

作者：Speer Thimoteus^*; Rohrer Lucia; Blyszczuk Przemyslaw; Shroff Rukshana; Kuschnerus Kira; Kraenkel Nicolle; Kania Gabriela; Zewinger Stephen; Akhmedov Alexander; Shi Yi; Martin Tina; Perisa Damir; Winnik Stephan; Mueller Maja F; Sester Urban; Wernicke Gabriel; Jung Andreas; Gutteck Ursula; Eriksson Urs; Geisel Juergen; Deanfield John; von Eckardstein Arnold; Luescher Thomas F; Fliser Danilo; Bahlmann Ferdinand H; Landmesser Ulf

来源：Immunity, 2013, 38(4): 754-768.

DOI：10.1016/j.immuni.2013.02.009

Endothelial injury and dysED) 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 dysHDLCKD), 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.

• 出版日期2013-4-18