Nielsen M H, Irvine H, Vedel S, Raungaard B, Beck-Nielsen H, Handberg A
Danish PhD School of Molecular Metabolism, University of Southern Denmark, 5000 Odense, Denmark; Department of Clinical Biochemistry, Aalborg University Hospital, 9000 Aalborg, Denmark.
Department of Medicine and Cardiology A, Aarhus University Hospital, 8000 Aarhus, Denmark.
Oxid Med Cell Longev. 2016;2016:2492858. doi: 10.1155/2016/2492858. Epub 2016 Jan 27.
Objective. Microvesicles (MVs) are small cell-derived particles shed upon activation. Familial hypercholesterolemia (FH) particularly when associated with Achilles tendon xanthomas (ATX) predisposes to atherosclerosis, possibly through oxLDL-C interaction with the CD36 receptor. To investigate the hypothesis that MVs derived from cells involved in atherosclerosis are increased in FH and that CD36 expressing MVs (CD36+ MVs) may be markers of oxLDL-C-induced cell activation, cell-specific MVs were measured in FH patients with and without ATX and their association with atherogenic lipid profile was studied. Approach and Results. Thirty FH patients with and without ATX and twenty-three controls were included. Plasma concentrations of MVs and CD36+ MVs derived from platelets (PMVs), erythrocytes (ErytMVs), monocytes (MMVs), and endothelial cells (EMVs), as well as tissue factor-positive cells (TF+ MVs), were measured by flow cytometry. Total MVs, MMVs, EMVs, ErytMVs, and TF+ MVs were significantly increased in FH patients, compared to controls. CD36+ MVs derived from endothelial cells and monocytes were significantly higher in FH patients and oxLDL-C predicted all the investigated cell-specific CD36+ MVs in FH patients with ATX. Conclusions. MVs derived from cells involved in atherosclerosis were increased in FH and may contribute to elevated atherothrombosis risk. The increased cell-specific CD36+ MVs observed in FH may represent markers of oxLDL-C-induced cell activation.
目的。微泡（MVs）是细胞激活时释放的小颗粒。家族性高胆固醇血症（FH），尤其是与跟腱黄瘤（ATX）相关时，易患动脉粥样硬化，可能是通过氧化型低密度脂蛋白胆固醇（oxLDL-C）与CD36受体相互作用导致。为了研究以下假设，即在FH中参与动脉粥样硬化的细胞衍生的MVs增加，且表达CD36的MVs（CD36 + MVs）可能是oxLDL-C诱导细胞激活的标志物，我们对有和没有ATX的FH患者的细胞特异性MVs进行了测量，并研究了它们与致动脉粥样硬化脂质谱的关联。方法与结果。纳入了30例有和没有ATX的FH患者以及23名对照。通过流式细胞术测量了源自血小板（PMVs）、红细胞（ErytMVs）、单核细胞（MMVs）和内皮细胞（EMVs）的MVs和CD36 + MVs的血浆浓度，以及组织因子阳性细胞（TF + MVs）的血浆浓度。与对照组相比，FH患者的总MVs、MMVs、EMVs、ErytMVs和TF + MVs显著增加。FH患者中源自内皮细胞和单核细胞的CD36 + MVs显著更高，并且oxLDL-C可预测有ATX的FH患者中所有研究的细胞特异性CD36 + MVs。结论。FH中参与动脉粥样硬化的细胞衍生的MVs增加，可能导致动脉粥样硬化血栓形成风险升高。在FH中观察到的细胞特异性CD36 + MVs增加可能代表oxLDL-C诱导细胞激活的标志物。
