College of Bioengineering, Henan University of Technology, Zhengzhou, China.
Apoptosis. 2012 Jan;17(1):25-36. doi: 10.1007/s10495-011-0653-6.
Vascular endothelial cell (VEC) apoptosis is the main event occurring during the development of atherosclerosis. Pterostilbene (PT), a natural dimethylated analog of resveratrol, has been the subject of intense research in cancer and inflammation. However, the protective effects of PT against oxidized low-density lipoprotein (oxLDL)-induced apoptosis in VECs have not been clarified. We investigated the anti-apoptotic effects of PT in vitro and in vivo in mice. PT at 0.1-5 μM possessed antioxidant properties comparable to that of trolox in a cell-free system. Exposure of human umbilical vein VECs (HUVECs) to oxLDL (200 μg/ml) induced cell shrinkage, chromatin condensation, nuclear fragmentation, and cell apoptosis, but PT protected against such injuries. In addition, PT injection strongly decreased the number of TUNEL-positive cells in the endothelium of atherosclerotic plaque from apoE(-/-) mice. OxLDL increased reactive oxygen species (ROS) levels, NF-κB activation, p53 accumulation, apoptotic protein levels and caspases-9 and -3 activities and decreased mitochondrial membrane potential (MMP) and cytochrome c release in HUVECs. These alterations were attenuated by pretreatment with PT. PT inhibited the expression of lectin-like oxLDL receptor-1 (LOX-1) expression in vitro and in vivo. Cotreatment with PT and siRNA of LOX-1 synergistically reduced oxLDL-induced apoptosis in HUVECs. Overexpression of LOX-1 attenuated the protection by PT and suppressed the effects of PT on oxLDL-induced oxidative stress. PT may protect HUVECs against oxLDL-induced apoptosis by downregulating LOX-1-mediated activation through a pathway involving oxidative stress, p53, mitochondria, cytochrome c and caspase protease. PT might be a potential natural anti-apoptotic agent for the treatment of atherosclerosis.
血管内皮细胞（VEC）凋亡是动脉粥样硬化发展过程中发生的主要事件。紫檀芪（PT）是白藜芦醇的天然二甲基化类似物，一直是癌症和炎症研究的热点。然而，PT 对氧化型低密度脂蛋白（oxLDL）诱导的 VEC 凋亡的保护作用尚未阐明。我们在体外和体内研究了 PT 对小鼠的抗凋亡作用。在无细胞系统中，0.1-5 μM 的 PT 具有与 Trolox 相当的抗氧化特性。将人脐静脉内皮细胞（HUVEC）暴露于 oxLDL（200μg/ml）会引起细胞收缩、染色质浓缩、核碎裂和细胞凋亡，但 PT 可防止这种损伤。此外，PT 注射可强烈减少载脂蛋白 E 基因敲除（apoE(-/-)）小鼠动脉粥样硬化斑块内皮中 TUNEL 阳性细胞的数量。oxLDL 增加活性氧（ROS）水平、NF-κB 激活、p53 积累、凋亡蛋白水平和 caspase-9 和 -3 活性，并降低线粒体膜电位（MMP）和细胞色素 c 释放。这些变化在 PT 预处理后减弱。PT 在体外和体内抑制凝集素样 oxLDL 受体-1（LOX-1）的表达。PT 和 LOX-1 的 siRNA 共同处理可协同减少 oxLDL 诱导的 HUVEC 凋亡。LOX-1 的过表达减弱了 PT 的保护作用，并抑制了 PT 对 oxLDL 诱导的氧化应激的影响。PT 可能通过下调 LOX-1 介导的激活来保护 HUVEC 免受 oxLDL 诱导的凋亡，该途径涉及氧化应激、p53、线粒体、细胞色素 c 和半胱天冬酶蛋白酶。PT 可能是治疗动脉粥样硬化的一种有前途的天然抗凋亡剂。
