ApoCIII-enriched LDL in type 2 diabetes displays altered lipid composition, increased susceptibility for sphingomyelinase, and increased binding to biglycan.
ApoCIII-enriched LDL in type 2 diabetes displays altered lipid composition, increased susceptibility for sphingomyelinase, and increased binding to biglycan.
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作者：
Hiukka A;Ståhlman M;Pettersson C;Levin M;Adiels M;Teneberg S;Leinonen ES;Hultén LM;Wiklund O;Oresic M;Olofsson SO;Taskinen MR;Ekroos K;Borén J
载脂蛋白CIII（apoCIII）是心血管疾病的独立危险因素，但其分子机制尚不清楚。我们研究了2型糖尿病高脂血症患者含apoCIII的LDL的潜在致动脉粥样硬化特性。从对照组、2型糖尿病患者和apoB转基因小鼠中分离LDL。使用包被有双糖蛋白聚糖的免疫板，通过固相测定分析LDL-双糖蛋白聚糖结合。用质谱法分析脂质组成。用[~ 3 H]鞘磷脂标记血浆LDL后，分析鞘磷脂酶对LDL的水解作用。等电聚焦后定量ApoCIII同种型。将人主动脉内皮细胞与去唾液酸化的apoCIII或与富含特定apoCIII同种型的LDL一起孵育。我们发现，丰富的低密度脂蛋白与apoCIII只诱导一个小的增加LDL-蛋白聚糖结合，这种效果是依赖于apoB 100的功能位点A。我们的研究结果表明，固有特性的糖尿病低密度脂蛋白以外的apoCIII负责进一步增加蛋白聚糖结合的糖尿病低密度脂蛋白与高内源性apoCIII，我们发现改变的脂质组成的糖尿病低密度脂蛋白与高apoCIII。我们还证明，高apoCIII增加了LDL对鞘磷脂酶水解和聚集的敏感性。此外，我们证明了apoCIII的唾液酸化随着apoCIII含量的增加而增加，并且apoCIII的唾液酸化对其促炎特性是必不可少的。我们已经证明了2型糖尿病高脂血症患者的含apoCIII的LDL的一些特征，这些特征可以解释apoCIII的促动脉粥样硬化作用。
Apolipoprotein CIII (apoCIII) is an independent risk factor for cardiovascular disease, but the molecular mechanisms involved are poorly understood. We investigated potential proatherogenic properties of apoCIII-containing LDL from hypertriglyceridemic patients with type 2 diabetes. LDL was isolated from control subjects, subjects with type 2 diabetes, and apoB transgenic mice. LDL-biglycan binding was analyzed with a solid-phase assay using immunoplates coated with biglycan. Lipid composition was analyzed with mass spectrometry. Hydrolysis of LDL by sphingomyelinase was analyzed after labeling plasma LDL with [3H]sphingomyelin. ApoCIII isoforms were quantified after isoelectric focusing. Human aortic endothelial cells were incubated with desialylated apoCIII or with LDL enriched with specific apoCIII isoforms. We showed that enriching LDL with apoCIII only induced a small increase in LDL-proteoglycan binding, and this effect was dependent on a functional site A in apoB100. Our findings indicated that intrinsic characteristics of the diabetic LDL other than apoCIII are responsible for further increased proteoglycan binding of diabetic LDL with high-endogenous apoCIII, and we showed alterations in the lipid composition of diabetic LDL with high apoCIII. We also demonstrated that high apoCIII increased susceptibility of LDL to hydrolysis and aggregation by sphingomyelinases. In addition, we demonstrated that sialylation of apoCIII increased with increasing apoCIII content and that sialylation of apoCIII was essential for its proinflammatory properties. We have demonstrated a number of features of apoCIII-containing LDL from hypertriglyceridemic patients with type 2 diabetes that could explain the proatherogenic role of apoCIII.
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影响因子：
2.9
作者：
AHMAD, TY;BEAUDET, AL;MORRISETT, JD
通讯作者：
MORRISETT, JD
影响因子：
2.9
作者：
IBDAH, JA;LUNDKATZ, S;PHILLIPS, MC
通讯作者：
PHILLIPS, MC
影响因子：
7.4
作者：
Ekroos, K;Chernushevich, IV;Shevchenko, A
通讯作者：
Shevchenko, A
DOI：
10.1161/01.atv.0000249620.68705.0d
发表时间：
2007-01-01
影响因子：
8.7
作者：
Kawakami, Akio;Aikawa, Masanori;Sacks, Frank M.
通讯作者：
Sacks, Frank M.
DOI：
10.1161/01.atv.0000117174.19078.85
发表时间：
2004-03-01
影响因子：
8.7
作者：
Flood, C;Gustafsson, M;Borén, J
通讯作者：
Borén, J