血浆血管生成素样蛋白 3 和 4 与血脂和代谢特征的差异关联。
Differential association of plasma angiopoietin-like proteins 3 and 4 with lipid and metabolic traits.
机构信息
From the Department of Medicine and Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (N.M., A.Q., L.Q., M.P.R., D.J.R.); Department of Medicine, University of California at San Francisco (A.N.Q.); and National Heart, Lung, and Blood Institute, Bethesda, MD (N.N.M.).
出版信息
Arterioscler Thromb Vasc Biol. 2014 May;34(5):1057-63. doi: 10.1161/ATVBAHA.113.302802. Epub 2014 Mar 13.
OBJECTIVE
Angiopoietin-like protein 3 (ANGPTL3) and 4 (ANGPTL4) are secreted proteins that inhibit lipoprotein lipase in vitro. Genetic variants at the ANGPTL3 and ANGPTL4 gene loci are significantly associated with plasma lipid traits. The aim of this study was to evaluate the association of plasma ANGPTL3 and ANGPTL4 concentrations with lipid and metabolic traits in a large community-based sample.
APPROACH AND RESULTS
Plasma ANGPTL3 and ANGPTL4 levels were measured in 1770 subjects using a validated ELISA assay. A Pearson unadjusted correlation analysis and a linear regression analysis adjusting for age, sex, and race were performed. ANGPTL3 levels were significantly positively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels (both P<2×10(-5)) but not triglycerides. In contrast, ANGPTL4 levels were significantly negatively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (both P<2×10(-5)) and positively associated with triglycerides (P=0.003). In addition, ANGPTL4, but not ANGPTL3, levels were significantly positively associated with fasting blood glucose and metabolic syndrome.
CONCLUSIONS
Despite having similar biochemical effects in vitro, plasma ANGPTL3 and ANGPTL4 concentrations have nearly opposite relationships with plasma lipids. ANGPTL4 is strongly negatively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol and positively with multiple features of the metabolic syndrome including triglycerides, whereas ANGPTL3 is positively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol and not with metabolic syndrome traits including triglycerides. Although ANGPTL3 and ANGPTL4 both inhibit lipoprotein lipase in vitro and influence lipoprotein metabolism in vivo, the physiology of these related proteins and their effects on lipoproteins is clearly divergent and complex.
目的
血管生成素样蛋白 3（ANGPTL3）和 4（ANGPTL4）是体外抑制脂蛋白脂肪酶的分泌蛋白。ANGPTL3 和 ANGPTL4 基因座的遗传变异与血浆脂质特征显著相关。本研究旨在评估大型社区样本中血浆 ANGPTL3 和 ANGPTL4 浓度与血脂和代谢特征的相关性。
方法和结果
使用经过验证的 ELISA 测定法测量了 1770 例患者的血浆 ANGPTL3 和 ANGPTL4 水平。进行了 Pearson 未调整的相关分析和线性回归分析，调整了年龄、性别和种族。ANGPTL3 水平与低密度脂蛋白胆固醇和高密度脂蛋白胆固醇水平呈显著正相关（均 P<2×10(-5)），但与甘油三酯无关。相比之下，ANGPTL4 水平与低密度脂蛋白胆固醇和高密度脂蛋白胆固醇呈显著负相关（均 P<2×10(-5)），与甘油三酯呈正相关（P=0.003）。此外，ANGPTL4 水平而不是 ANGPTL3 水平与空腹血糖和代谢综合征显著正相关。
结论
尽管在体外具有相似的生化作用，但血浆 ANGPTL3 和 ANGPTL4 浓度与血浆脂质几乎呈相反关系。ANGPTL4 与低密度脂蛋白胆固醇和高密度脂蛋白胆固醇呈强烈负相关，与代谢综合征的多种特征（包括甘油三酯）呈正相关，而 ANGPTL3 与低密度脂蛋白胆固醇和高密度脂蛋白胆固醇呈正相关，与代谢综合征特征（包括甘油三酯）无关。尽管 ANGPTL3 和 ANGPTL4 在体外均抑制脂蛋白脂肪酶并影响体内脂蛋白代谢，但这些相关蛋白的生理学及其对脂蛋白的影响显然是不同的且复杂的。
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