Strang Aart C, Knetsch Menno L W, Koole Leo H, de Winter Robbert J, van der Wal Allard C, de Vries Carlie J M, Tak Paul P, Bisoendial Radjesh J, Stroes Erik S G, Rotmans Joris I
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Department of Biomedical Engineering/Biomaterials Science, Maastricht University, Maastricht, The Netherlands.
PLoS One. 2015 Mar 30;10(3):e0122836. doi: 10.1371/journal.pone.0122836. eCollection 2015.
Since high-density lipoprotein (HDL) has pro-endothelial and anti-thrombotic effects, a HDL recruiting stent may prevent restenosis. In the present study we address the functional characteristics of an apolipoprotein A-I (ApoA-I) antibody coating in vitro. Subsequently, we tested its biological performance applied on stents in vivo in rabbits.
The impact of anti ApoA-I- versus apoB-antibody coated stainless steel discs were evaluated in vitro for endothelial cell adhesion, thrombin generation and platelet adhesion. In vivo, response to injury in the iliac artery of New Zealand white rabbits was used as read out comparing apoA-I-coated versus bare metal stents.
ApoA-I antibody coated metal discs showed increased endothelial cell adhesion and proliferation and decreased thrombin generation and platelet adhesion, compared to control discs. In vivo, no difference was observed between ApoA-I and BMS stents in lumen stenosis (23.3±13.8% versus 23.3±11.3%, p=0.77) or intima surface area (0.81±0.62 mm2 vs 0.84±0.55 mm2, p=0.85). Immunohistochemistry also revealed no differences in cell proliferation, fibrin deposition, inflammation and endothelialization.
ApoA-I antibody coating has potent pro-endothelial and anti-thrombotic effects in vitro, but failed to enhance stent performance in a balloon injury rabbit model in vivo.
由于高密度脂蛋白(HDL)具有促进内皮细胞生长和抗血栓形成的作用,一种能募集HDL的支架可能预防再狭窄。在本研究中,我们探讨了载脂蛋白A-I(ApoA-I)抗体涂层在体外的功能特性。随后,我们在兔体内测试了其应用于支架的生物学性能。
体外评估抗ApoA-I抗体与抗载脂蛋白B(apoB)抗体涂层不锈钢圆盘对内皮细胞黏附、凝血酶生成和血小板黏附的影响。在体内,以新西兰白兔髂动脉损伤反应作为观察指标,比较ApoA-I涂层支架与裸金属支架。
与对照圆盘相比,ApoA-I抗体涂层金属圆盘显示出内皮细胞黏附与增殖增加,凝血酶生成与血小板黏附减少。在体内,ApoA-I支架与裸金属支架在管腔狭窄(23.3±13.8%对23.3±11.3%,p = 0.77)或内膜表面积(0.81±0.62mm²对0.84±0.55mm²,p = 0.85)方面未观察到差异。免疫组织化学也显示在细胞增殖、纤维蛋白沉积、炎症和内皮化方面无差异。
ApoA-I抗体涂层在体外具有强大的促内皮细胞生长和抗血栓形成作用,但在兔体内球囊损伤模型中未能增强支架性能。