Mineo Chieko, Shaul Philip W
Department of Pediatrics, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Trends Cardiovasc Med. 2003 Aug;13(6):226-31. doi: 10.1016/s1050-1738(03)00098-7.
High-density lipoprotein (HDL), apolipoprotein A-I (apoA-I), and the principal high-affinity HDL receptor, scavenger receptor class B type I (SR-BI), are antiatherogenic and beneficial to the response to vascular injury. However, the fundamental mechanisms underlying these properties remain complex and not well understood. Recent work in both cell culture and in mice indicates that HDL causes robust activation of endothelial nitric oxide synthase (eNOS), and that this effect is mediated in endothelial cell caveolae by SR-BI through a process that requires apoA-I binding. Further studies have revealed that HDL stimulates eNOS through src- and PI3 kinase-mediated signaling, which leads to parallel activation of Akt and mitogen-activated protein kinases and their resultant independent modulation of the enzyme. As such, signaling initiated by HDL increases the production of the potent atheroprotective molecule nitric oxide, and this novel mechanism of action may be critically involved in the impact of the lipoprotein on vascular health and disease.
高密度脂蛋白（HDL）、载脂蛋白A-I（apoA-I）以及主要的高亲和力HDL受体，即B类I型清道夫受体（SR-BI），具有抗动脉粥样硬化作用，且有利于对血管损伤的反应。然而，这些特性背后的基本机制仍然复杂，尚未完全明确。近期在细胞培养和小鼠实验中的研究表明，HDL可强力激活内皮型一氧化氮合酶（eNOS），且这种效应在内皮细胞小窝中由SR-BI介导，通过一个需要apoA-I结合的过程实现。进一步研究发现，HDL通过src和PI3激酶介导的信号传导刺激eNOS，这导致Akt和丝裂原活化蛋白激酶的平行激活以及它们对该酶的独立调节。因此，HDL引发的信号传导增加了强效抗动脉粥样硬化分子一氧化氮的生成，这种新的作用机制可能在脂蛋白对血管健康和疾病的影响中起关键作用。
