Different relationship between ANGPTL3 and HDL components in female non-diabetic subjects and type-2 diabetic patients.
Different relationship between ANGPTL3 and HDL components in female non-diabetic subjects and type-2 diabetic patients.
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女性非糖尿病受试者和 2 型糖尿病患者中 ANGPTL3 和 HDL 成分之间的不同关系。
DOI：
10.1186/s12933-016-0450-1
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发表时间：
2016-09-13
影响因子：
9.3
通讯作者：
Feng YM
中科院分区：
文献类型：
--
作者：
Zhao D;Yang LY;Wang XH;Yuan SS;Yu CG;Wang ZW;Lang JN;Feng YM
血管生成素样蛋白3（ANGPTL 3）是一种主要的脂蛋白调节剂，在人群研究和ANGPTL 3突变受试者中显示与高密度脂蛋白胆固醇（HDL-c）正相关。然而，没有研究表明它与HDL组分或HDL功能在2型糖尿病（T2 DM）患者中的相关性。我们研究了298名非糖尿病受试者和300名T2 DM患者，他们是在三级转诊中心随机招募的。通过ELISA定量ANGPTL 3的血浆水平。分离血浆样品以获得HDL。测定高密度脂蛋白（HDL）的载脂蛋白A-I（apoA-I）、甘油三酯、血清淀粉样蛋白A（SAA）、磷脂和1-磷酸鞘氨醇。通过超离心法从女性对照和T2 DM患者中分离HDL，以评估胆固醇对HDL的流出。在男性或女性非糖尿病参与者或糖尿病患者中分别进行了Pearson未校正相关分析和调整年龄、体重指数和降脂药物的线性回归分析。我们证明女性T2 DM患者的血浆ANGPTL 3水平低于女性对照，尽管男性对照和T2 DM患者之间没有检测到ANGPTL 3水平的差异。在调整混杂因素后，ANGPTL 3（164.6 ng/ml）增加一个SD与非糖尿病女性HDL颗粒中胆固醇增加2.57 mg/dL和apoA-I增加1.14 μg/mL相关，但SAA减少47.07 μg/L（胆固醇和SAA p < 0.05; apoA-I p < 0.0001）。相比之下，ANGPTL 3（159.9 ng/ml）的1-SD增加与女性糖尿病患者HDL颗粒中1.69 mg/dl胆固醇和1.25 μg/mL apoA-I的增加相关，但SAA减少11.70 μg/L（胆固醇p < 0.05; apoA-I p < 0.0001; SAA p = 0.676）。此外，ANGPTL 3增加一个SD与非糖尿病女性中相对于HDL的胆固醇流出增加2.11%（p = 0.071）相关，但在调整混杂因素后，女性T2 DM患者中降低1.46%（p = 0.13）。ANGPTL 3与女性非糖尿病参与者中的HDL-c、apoA-I、SAA和HDL功能特异性相关。女性T2 DM患者ANGPTL 3水平的降低可能与其与HDL组分和功能的弱相关性有关。ANGPTL 3可能被认为是治疗糖尿病的HDL代谢的新的治疗靶点。本文的在线版本（doi：10.1186/s12933-016-0450-1）包含补充材料，可供授权用户使用。
Angiopoietin-like protein 3 (ANGPTL3) is a major lipoprotein regulator and shows positive correlation with high-density lipoprotein-cholesterol (HDL-c) in population studies and ANGPTL3 mutated subjects. However, no study has looked its correlation with HDL components nor with HDL function in patients with type 2 diabetes mellitus (T2DM). We studied 298 non-diabetic subjects and 300 T2DM patients who were randomly recruited in the tertiary referral centre. Plasma levels of ANGPTL3 were quantified by ELISA. Plasma samples were fractionated to obtain HDLs. HDL components including apolipoprotein A-I (apoA-I), triglyceride, serum amyloid A (SAA), phospholipid and Sphingosine-1-phosphate were measured. HDLs were isolated from female controls and T2DM patients by ultracentrifugation to assess cholesterol efflux against HDLs. A Pearson unadjusted correlation analysis and a linear regression analysis adjusting for age, body mass index and lipid lowering drugs were performed in male or female non-diabetic participants or diabetic patients, respectively. We demonstrated that plasma level of ANGPTL3 was lower in female T2DM patients than female controls although no difference of ANGPTL3 levels was detected between male controls and T2DM patients. After adjusting for confounding factors, one SD increase of ANGPTL3 (164.6 ng/ml) associated with increase of 2.57 mg/dL cholesterol and 1.14 μg/mL apoA-I but decrease of 47.07 μg/L of SAA in HDL particles of non-diabetic females (p < 0.05 for cholesterol and SAA; p < 0.0001 for apoA-I). By contrast, 1-SD increase of ANGPTL3 (159.9 ng/ml) associated with increase of 1.69 mg/dl cholesterol and 1.25 μg/mL apoA-I but decrease of 11.70 μg/L of SAA in HDL particles of female diabetic patients (p < 0.05 for cholesterol; p < 0.0001 for apoA-I; p = 0.676 for SAA). Moreover, one SD increase of ANGPTL3 associated with increase of 2.11 % cholesterol efflux against HDLs in non-diabetic females (p = 0.071) but decrease of 1.46 % in female T2DM patients (p = 0.13) after adjusting for confounding factors. ANGPTL3 is specifically correlated with HDL-c, apoA-I, SAA and HDL function in female non-diabetic participants. The decrease of ANGPTL3 level in female T2DM patients might contribute to its weak association to HDL components and function. ANGPTL3 could be considered as a novel therapeutic target for HDL metabolism for treating diabetes. The online version of this article (doi:10.1186/s12933-016-0450-1) contains supplementary material, which is available to authorized users.
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DOI：
10.1161/atvbaha.113.302802
发表时间：
2014-05
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Mehta N;Qamar A;Qu L;Qasim AN;Mehta NN;Reilly MP;Rader DJ
通讯作者：
Rader DJ
影响因子：
37.8
作者：
Calkin, Anna C.;Drew, Brian G.;Jackson, Shaun P.
通讯作者：
Jackson, Shaun P.
影响因子：
3.1
作者：
Liu, SB;Gallo, DJ;Billiar, TR
通讯作者：
Billiar, TR
DOI：
10.1056/nejmoa1002926
发表时间：
2010-12-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
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通讯作者：
Kathiresan S
影响因子：
30.8
作者：
Koishi, R;Ando, Y;Furukawa, H
通讯作者：
Furukawa, H