Bochkov Valery N, Philippova Maria, Oskolkova Olga, Kadl Alexandra, Furnkranz Alexander, Karabeg Erduan, Afonyushkin Taras, Gruber Florian, Breuss Johannes, Minchenko Alexander, Mechtcheriakova Diana, Hohensinner Philipp, Rychli Kathrin, Wojta Johann, Resink Therese, Erne Paul, Binder Bernd R, Leitinger Norbert
Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria.
Circ Res. 2006 Oct 13;99(8):900-8. doi: 10.1161/01.RES.0000245485.04489.ee. Epub 2006 Sep 14.
Angiogenesis is a common feature observed in advanced atherosclerotic lesions. We hypothesized that oxidized phospholipids (OxPLs), which accumulate in atherosclerotic vessels can stimulate angiogenesis. We found that oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) stimulated the formation of sprouts from endothelial cell spheroids and promoted growth of capillaries into Matrigel plugs in mice. OxPLs stimulated expression of vascular endothelial growth factor (VEGF) in vivo and in several normal and tumor cell types in vitro. In addition, OxPAPC upregulated cyclooxygenase (COX)-2 and interleukin (IL)-8. COX-2 inhibitors, as well as blocking antibodies to IL-8 suppressed activation of sprouting by OxPAPC. We conclude that OxPAPC stimulates angiogenesis via autocrine mechanisms involving VEGF, IL-8, and COX-2-generated prostanoids. Our data suggest that accumulation of OxPLs may contribute to increased growth of blood capillaries in advanced lesions, thus leading to progression and destabilization of atherosclerotic plaques.
血管生成是在晚期动脉粥样硬化病变中观察到的一个常见特征。我们推测，在动脉粥样硬化血管中积累的氧化磷脂（OxPLs）可以刺激血管生成。我们发现，氧化1-棕榈酰-2-花生四烯酰-sn-甘油-3-磷酸胆碱（OxPAPC）刺激内皮细胞球体形成芽，并促进小鼠毛细血管向基质胶栓中生长。OxPLs在体内以及几种正常和肿瘤细胞类型中体外刺激血管内皮生长因子（VEGF）的表达。此外，OxPAPC上调环氧化酶（COX）-2和白细胞介素（IL）-8。COX-2抑制剂以及抗IL-8阻断抗体抑制了OxPAPC对芽形成的激活。我们得出结论，OxPAPC通过涉及VEGF、IL-8和COX-2产生的前列腺素的自分泌机制刺激血管生成。我们的数据表明，OxPLs的积累可能有助于晚期病变中毛细血管生长增加，从而导致动脉粥样硬化斑块的进展和不稳定。
