Evidence for a complex relationship between apoA-V and apoC-III in patients with severe hypertriglyceridemia

Evidence for a complex relationship between apoA-V and apoC-III in patients with severe hypertriglyceridemia
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DOI:
10.1194/jlr.m500533-jlr200
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发表时间:
2006-10-01
影响因子:
6.5
通讯作者:
Groen, Albert K.
Groen, Albert K.
中科院分区:
生物学2区
文献类型:
--
作者:
Schaap, Frank G.;Nierman, Melchior C.;Groen, Albert K.

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载脂蛋白A-V(apoA-V)与人类脂质稳态的相关性通过遗传关联研究和APOA 5基因截短突变的鉴定得到强调,该突变是V型高脂血症的原因,与apoA-V的LPL激活作用相一致。从动物数据推测血浆apoA-V与甘油三酯(TG)水平之间存在负相关性。然而,最近在人类受试者中使用(半)定量免疫测定法的研究没有为这种关系提供明确的支持。在这里,我们使用了一种新的,验证ELISA测定血浆载脂蛋白A-V水平的患者(n = 28)与高脂血症(HTG; 1.8-78.7 mmol TG/l)和正常血脂对照组(n = 42)。出乎意料的是,与对照组相比,HTG受试者的血浆apoA-V水平显著升高(1,987对258 ng/ml; P < 0.001)。HTG组apoA-V与TG呈正相关(r =+0.44,P = 0.02)。此外,我们注意到HTG组的LPL抑制蛋白apoC-III水平升高(45.8 mg/dl vs.对照组的10.6 mg/dl; P < 0.001)。当控制apoC-III水平时,HTG组中apoA-V与TG水平之间的相关性消失(部分r = 10.09,P = 0.65)。相反,当控制apoA-V时,apoC-III和TG在该组中保持正相关(部分r =+0.43,P = 0.025)。我们的研究结果表明,在HTG患者中,TG水平升高伴随着apoA-V和apoC-III的高血浆水平,apoA-V和apoC-III是具有相反作用模式的载脂蛋白。本研究为严重HTG患者中apoA-V和apoC-III之间复杂的相互作用提供了证据。- Schaap,F. G.,M. C.尼尔曼,J.F. P. Berbee,H. Hattori,P. J. Talmud,S. F. C.韦森省N. Rensen,R.A.F.M. Chamuleau,J. A. Kuivenhoven和A. K.格伦严重高脂血症患者apoA-V和apoC-III之间复杂关系的证据
The relevance of apolipoprotein A-V (apoA-V) for human lipid homeostasis is underscored by genetic association studies and the identification of truncation-causing mutations in the APOA5 gene as a cause of type V hyper-lipidemia, compatible with an LPL-activating role of apoA-V. An inverse correlation between plasma apoA-V and triglyceride (TG) levels has been surmised from animal data. Recent studies in human subjects using (semi) quantitative immunoassays, however, do not provide unambiguous support for such a relationship. Here, we used a novel, validated ELISA to measure plasma apoA-V levels in patients (n = 28) with hypertriglyceridemia (HTG; 1.8-78.7 mmol TG/l) and normolipidemic controls (n = 42). Unexpectedly, plasma apoA-V levels were markedly increased in the HTG subjects compared with controls (1,987 vs. 258 ng/ml; P < 0.001). In the HTG group, apoA-V and TG were positively correlated (r = +0.44, P = 0.02). In addition, we noted an increased level of the LPL-inhibitory protein apoC-III in the HTG group (45.8 vs. 10.6 mg/dl in controls; P < 0.001). The correlation between apoA-V and TG levels in the HTG group disappeared (partial r = 10.09, P = 0.65) when controlling for apoC-III levels. In contrast, apoC-III and TG remained positively correlated in this group when controlling for apoA-V (partial r = +0.43, P = 0.025).jlr Our findings suggest that in HTG patients, increased TG levels are accompanied by high plasma levels of apoA-V and apoC-III, apolipoproteins with opposite modes of action. This study provides evidence for a complex interaction between apoA-V and apoC-III in patients with severe HTG. - Schaap, F. G., M. C. Nierman, J. F. P. Berbee, H. Hattori, P. J. Talmud, S. F. C. Vaessen, P. C. N. Rensen, R.A.F.M. Chamuleau, J. A. Kuivenhoven, and A. K. Groen. Evidence for a complex relationship between apoA-V and apoC-III in patients with severe hypertriglyceridemia.