Apolipoprotein CIII in apolipoprotein B lipoproteins enhances the adhesion of human monocytic cells to endothelial cells
Apolipoprotein CIII in apolipoprotein B lipoproteins enhances the adhesion of human monocytic cells to endothelial cells
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DOI：
10.1161/circulationaha.105.591743
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发表时间：
2006-02-07
期刊：
影响因子：
37.8
通讯作者：
Sacks, FM
中科院分区：
文献类型：
--
作者：
Kawakami, A;Aikawa, M;Sacks, FM
背景--含有载脂蛋白(Apo)CIII的脂蛋白可预测冠心病，并与代谢综合征的组成部分相关。APOCIII抑制血浆脂蛋白分解代谢。然而，目前尚不清楚载脂蛋白CIII本身或与极低密度脂蛋白、低密度脂蛋白或高密度脂蛋白联合作用是否直接影响血管细胞的动脉粥样硬化形成机制。因此，我们研究了有或没有apoCIII的脂蛋白以及apoCIII本身对人单核细胞系THP-1细胞与血管内皮细胞(ECs)黏附的直接影响。方法和结果-18名正常血脂志愿者空腹血浆中的VLDLCIII+和LDLCIII+(100mU g apoB/mL)在静态条件下使THP-1细胞与ECs的黏附分别增加2.4+/-0.3倍和1.8+/-0.7倍(P<；0.01)，而VLDL或不含apoCIII的低密度脂蛋白对THP-1细胞黏附无影响。ApoC III(100 mU g/m L)可使THP-1细胞黏附率提高2.1+/-0.6倍，而apoCI、apoCII或apoE则无此作用。对人类外周血单核细胞的研究也得出了类似的结果。APOCIII在剪切流动条件下也有很强的前黏附作用。VLDLCIII+、LDLCIII+或apoCIII自身激活了THP-1细胞中的PKCα和RhoA，从而导致β1整合素的激活，增强了THP-1细胞的粘附性。有趣的是，高密度脂蛋白CIII+不影响THP-1细胞与内皮细胞的黏附，而不含apoCIII的高密度脂蛋白降低了THP-1细胞与内皮细胞的黏附。这些结果表明，apoCIII不仅调节脂蛋白代谢，而且可能直接参与动脉粥样硬化的发展。
Background - Lipoproteins containing apolipoprotein (apo) CIII predict coronary heart disease and associate with components of the metabolic syndrome. ApoCIII inhibits lipoprotein catabolism in plasma. However, it is unknown whether apoCIII itself, or in association with VLDL, LDL, or HDL, directly affects atherogenic mechanisms in vascular cells. Thus, we investigated the direct effect of lipoproteins that do or do not have apoCIII, and apoCIII itself, on adhesion of THP-1 cells, a human monocytic cell line, to vascular endothelial cells (ECs).Methods and Results - VLDL CIII+ and LDL CIII+ (100 mu g apoB/mL) from fasting plasma of 18 normolipidemic volunteers increased THP-1 cell adhesion to ECs under static conditions by 2.4 +/- 0.3-fold and 1.8 +/- 0.7-fold, respectively (P < 0.01), whereas VLDL or LDL without apoCIII did not affect THP-1 cell adhesion. ApoCIII (100 mu g/mL), but not apoCI, apoCII or apoE, also increased THP-1 cell adhesion by 2.1 +/- 0.6-fold. Studies with human peripheral blood monocytes yielded similar results. ApoCIII also had strong proadhesive effects under shear flow conditions. VLDL CIII+, LDL CIII+, or apoCIII itself activated PKC alpha and RhoA in THP-1 cells, which resulted in beta 1-integrin activation and enhancement of THP-1 cell adhesion. Interestingly, HDL CIII+ did not affect THP-1 cell adhesion, whereas HDL without apoCIII decreased their adhesion.Conclusions - ApoB lipoproteins that contain apoCIII increase THP-1 cell adhesion to ECs via PKC alpha and RhoA-mediated beta 1-integrin activation. These results indicate that apoCIII not only modulates lipoprotein metabolism but also may directly contribute to the development of atherosclerosis.