Metabolic syndrome features small, apolipoprotein A-I-poor, triglyceride-rich HDL3 particles with defective anti-apoptotic activity
Metabolic syndrome features small, apolipoprotein A-I-poor, triglyceride-rich HDL3 particles with defective anti-apoptotic activity
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DOI：
10.1016/j.atherosclerosis.2007.08.009
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发表时间：
2008-03-01
期刊：
影响因子：
5.3
通讯作者：
Kontush, Anatol
中科院分区：
文献类型：
--
作者：
de Souza, Juliana A.;Vindis, Cecile;Kontush, Anatol
代谢综合征（MetS）表型的典型特征是内脏肥胖、胰岛素抵抗、动脉粥样硬化性血脂异常（包括高甘油三酯血症和高密度脂蛋白-胆固醇（HDL-C）亚正常水平）、氧化应激和心血管风险升高。小HDL3的有效抗氧化活性在met中是缺陷的[Hansel B，等]。中西医结合杂志[J]; 2009; 29(3): 391 - 391。我们评估了来自MetS受试者的小HDL3颗粒保护内皮细胞免受轻度氧化低密度脂蛋白（oxLDL）诱导的凋亡的功能能力。MetS受试者表现为胰岛素抵抗型肥胖表型，伴有高甘油三酯血症，载脂蛋白B和胰岛素水平升高，但HDL-C浓度低于正常水平，慢性低度炎症（c反应蛋白升高三倍）。当人微血管内皮细胞（HMEC-1）与oxLDL （200 μ g载脂蛋白B/ml）孵育时，无论是否存在对照HDL亚群（25 μ g蛋白/ml），小而致密的HDL3b和3c显著抑制细胞膜联蛋白V的结合和细胞内活性氧的产生。与正常血脂对照组（n = 7）相比，MetS受试者（n = 16）的小HDL3c颗粒的有效抗凋亡活性降低（-35%;p < 0.05）。HDL3c抗凋亡活性减弱与腹部肥胖、动脉粥样硬化性血脂异常和全身氧化应激相关（p < 0.05），并与载脂蛋白A-I （apoA-I-poor HDL3c）的理化性质改变密切相关，包括核心胆固醇酯消耗和甘油三酯富集。我们得出结论，在MetS中，apoa -i缺乏、小而致密的HDL3c对内皮细胞免于氧化低密度脂蛋白诱导的凋亡的保护存在缺陷，这可能反映了与异常中性脂核含量密切相关的功能异常。2007爱思唯尔爱尔兰有限公司版权所有。
The metabolic syndrome (MetS) phenotype is typically characterized by visceral obesity, insulin resistance, atherogenic dyslipidemia involving hypertriglyceridemia and subnormal levels of high density lipoprotein-cholesterol (HDL-C), oxidative stress and elevated cardiovascular risk. The potent antioxidative activity of small HDL3 is defective in MetS [Hansel B, et al. J Clin Endocrinol Metab 2004;89:4963-71]. We evaluated the functional capacity of small HDL3 particles from MetS subjects to protect endothelial cells from apoptosis induced by mildly oxidized low-density lipoprotein (oxLDL).MetS subjects presented an insulin-resistant obese phenotype, with hypertriglyceridemia, elevated apolipoprotein B and insulin levels, but subnormal HDL-C concentrations and chronic low grade inflammation (threefold elevation of C-reactive protein). When human microvascular endothelial cells (HMEC-1) were incubated with oxLDL (200 jig apolipoprotein B/ml) in the presence or absence of control HDL subfiractions (25 mu g protein/ml), small, dense HDL3b and 3c significantly inhibited cellular annexin V binding and intracellular generation of reactive oxygen species. The potent anti-apoptotic activity of small HDL3c particles was reduced (-35%; p < 0.05) in MetS subjects (n = 16) relative to normolipidemic controls (n = 7). The attenuated anti-apoptotic activity of HDL3c correlated with abdominal obesity, atherogenic dyslipidemia and systemic oxidative stress (p < 0.05), and was intimately associated with altered physicochemical properties of apolipoprotein A-I (apoA-I-poor HDL3c, involving core cholesteryl ester depletion and triglyceride enrichment.We conclude that in MetS, apoA-I-poor, small, dense HDL3c exert defective protection of endothelial cells from oxLDL-induced apoptosis, potentially reflecting functional anomalies intimately associated with abnormal neutral lipid core content. (c) 2007 Elsevier Ireland Ltd. All rights reserved.