Poon M, Zhang X, Dunsky K G, Taubman M B, Harpel P C
Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
Circulation. 1997 Oct 21;96(8):2514-9. doi: 10.1161/01.cir.96.8.2514.
Elevated levels of lipoprotein(a) [Lp(a)] are associated with premature atherosclerosis; however, the mechanisms are not known. Recruitment of monocytes to the blood vessel wall is an early event in atherogenesis.
This study has found that unoxidized Lp(a) induced human umbilical vein endothelial cells (HUVECs) to secrete monocyte chemotactic activity (MCA), whereas LDL under the same conditions did not. In the absence of HUVECs, Lp(a) had no direct MCA. Endotoxin was shown not to be responsible for the induction of MCA. Actinomycin D and cycloheximide inhibited the HUVEC response to Lp(a), indicating that protein and RNA synthesis were required. The apolipoprotein(a) [apo(a)] portion of Lp(a) was identified as the structural component of Lp(a) responsible for inducing MCA. Lp(a) and apo(a) also stimulated human coronary artery endothelial cells to produce MCA. Granulocyte-monocyte colony-stimulating factor (GM-CSF) antigen was not detected in the Lp(a)-conditioned medium, nor was monocyte chemoattractant protein-1 mRNA induced in HUVECs by Lp(a).
These findings suggest that Lp(a) may be involved in the recruitment of monocytes to the vessel wall and provide a novel mechanism for the participation of Lp(a) in the atherogenic process.
脂蛋白(a)[Lp(a)]水平升高与动脉粥样硬化提前发生有关；然而，其机制尚不清楚。单核细胞募集到血管壁是动脉粥样硬化发生的早期事件。
本研究发现，未氧化的Lp(a)可诱导人脐静脉内皮细胞(HUVECs)分泌单核细胞趋化活性(MCA)，而相同条件下的低密度脂蛋白(LDL)则不能。在没有HUVECs的情况下，Lp(a)没有直接的MCA。内毒素被证明与MCA的诱导无关。放线菌素D和放线菌酮抑制HUVECs对Lp(a)的反应，表明需要蛋白质和RNA合成。Lp(a)的载脂蛋白(a)[apo(a)]部分被确定为Lp(a)诱导MCA的结构成分。Lp(a)和apo(a)也刺激人冠状动脉内皮细胞产生MCA。在Lp(a)条件培养基中未检测到粒细胞-单核细胞集落刺激因子(GM-CSF)抗原，Lp(a)也未诱导HUVECs中的单核细胞趋化蛋白-1 mRNA。
这些发现表明，Lp(a)可能参与单核细胞向血管壁的募集，并为Lp(a)参与动脉粥样硬化形成过程提供了一种新机制。
