Diabetic LDL triggers apoptosis in vascular endothelial cells
Diabetic LDL triggers apoptosis in vascular endothelial cells
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DOI：
10.2337/diabetes.52.5.1240
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发表时间：
2003-05-01
期刊：
影响因子：
7.7
通讯作者：
Baumgartner-Parzer, SM
中科院分区：
文献类型：
--
作者：
Artwohl, M;Graier, WF;Baumgartner-Parzer, SM
本研究比较了体外糖化LDL（LDLiv）或体内糖化LDL（LDLD）对培养的人脐静脉内皮细胞凋亡、增殖和相关蛋白表达的影响。在100 mg/l时，与个体内非糖化LDL亚组分相比，两种LDL均显著增加细胞凋亡（LDLiv 63%，LDLD 40%; P < 0.05）。考虑到其糖基化程度较低（LDLD 5- 10%，LDLiv 42%），LDLD的相对促凋亡活性是LDLiv的2.7倍。糖化LDL诱导的细胞凋亡与细胞凋亡促进剂的表达增加相关（LDLiv：巴克88%，CPP-32 49%; LDLD：巴克18%，CPP-32 11%; P < 0.05），并被半胱天冬酶抑制剂减弱。糖化低密度脂蛋白的抗增殖活性（LDLiv-34%，LDLD-9%; P < 0.01）与减少有关细胞周期蛋白D3（P < 0.05）（LDLiv-27%，LDLD-24%）和hypo-（LDLiv-22%，LDLD-19%）和过度磷酸化（LDLiv-53%，LDLD-22%）的视网膜母细胞瘤蛋白的表达，并通过减少内皮型一氧化氮合酶的表达（LDLiv-30%，LDLD-23%）来抑制。在响应脂蛋白脂酶，LDLD更明显地触发内皮细胞凋亡（27.1倍）相比，LDLiv，这表明LDLD具有更高的潜力，内皮细胞损伤比LDLiv。观察到的LDLD与LDLiv的行为可能具有临床意义，并且与LDLD与LDLiv相比的结构和细胞摄取差异密切相关。
This study compares the effects of LDL glycated either in vitro (LDLiv or in vivo in diabetic patients (LDLD) on apoptosis, proliferation, and associated protein expression in cultured human umbilical vein endothelial cells. At 100 mg/l, both LDL species considerably increase apoptosis (LDLiv 63%, LDLD 40%; P < 0.05) compared with intraindividual nonglycated LDL subfractions. Considering its lower degree of glycation (LDLD 5-10%, LDLiv 42%), LDLD's relative proapoptotic activity is 2.7-fold greater than that of LDLiv. Glycated LDL-induced apoptosis is associated with increased expression of apoptosis promotors (LDLiv: bak 88%, CPP-32 49%; LDLD: bak 18%, CPP-32 11%; P < 0.05) and is attenuated by caspase inhibitors. Glycated LDL's antiproliferative activity (LDLiv -34%, LDLD -9%; P < 0.01) relates to reduction (P < 0.05) of cyclin D3 (LDLiv -27%, LDLD -24%) and of hypo- (LDLiv -22%, LDLD -19%) and hyperphosphorylated (LDLiv -53%, LDLD -22%) retinoblastoma protein and is paralleled by reduced expression of endothelial nitric oxide synthase (LDLiv -30%, LDLD -23%). In response to lipoprotein lipase, LDLD more markedly triggers endothelial apoptosis (27.1-fold) compared with LDLiv, suggesting that LDLD owns a higher potential for endothelial cell damage than LDLiv. The observed behavior of LDLD versus LDLiv, could be of clinical importance and well relate to differences in structure and cellular uptake of LDLD compared with LDLiv.