Institute of Vascular Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.
Biochem Biophys Res Commun. 2011 Apr 1;407(1):44-8. doi: 10.1016/j.bbrc.2011.02.096. Epub 2011 Feb 23.
It has long been considered that oxidized low-density lipoprotein (oxLDL) causes endothelial dysfunction and is remarkably related to the development of atherosclerosis. However, the effect of oxLDL at very low concentration (<10μg/ml) on the endothelial cells remains speculative. Nitric oxide (NO) has a crucial role in the endothelial cell function. In this study, we investigated the effect of oxLDL at low concentration on NO production and proliferation, migration, tube formation of the human coronary artery endothelial cells (HCAEC). Results showed that oxLDL at 5μg/ml enhanced HCAEC proliferation, migration and tube formation. These phenomena were accompanied by an increased intracellular NO production. l-NAME (a NOS inhibitor), LY294002 and wortmannin (PI3K inhibitors) could abolish oxLDL-induced angiogenic effects and prevent NO production in the HCAEC. The phosphorylation of Akt, PI3K and eNOS were up-regulated by oxLDL, which was attenuated by LY294002. Our results suggested that oxLDL at low concentration could promote in-vitro angiogenesis and activate nitric oxide synthesis through PI3K/Akt/eNOS pathway in HCAEC.
一直以来，人们认为氧化型低密度脂蛋白（oxLDL）可导致血管内皮功能障碍，与动脉粥样硬化的发生发展显著相关。然而，oxLDL 在极低浓度（<10μg/ml）时对血管内皮细胞的作用仍存在推测。一氧化氮（NO）在血管内皮细胞功能中起着至关重要的作用。在这项研究中，我们研究了低浓度 oxLDL 对人冠状动脉内皮细胞（HCAEC）NO 产生、增殖、迁移和管状结构形成的影响。结果表明，5μg/ml 的 oxLDL 可增强 HCAEC 的增殖、迁移和管状结构形成。这些现象伴随着细胞内 NO 产生的增加。NOS 抑制剂 l-NAME、PI3K 抑制剂 LY294002 和 wortmannin 可消除 oxLDL 诱导的血管生成作用，并阻止 HCAEC 中 NO 的产生。oxLDL 可使 Akt、PI3K 和 eNOS 磷酸化增加，而 LY294002 可减弱这种作用。我们的结果表明，低浓度的 oxLDL 可通过 HCAEC 中的 PI3K/Akt/eNOS 通路促进体外血管生成并激活一氧化氮合成。
