Sonowal Himangshu, Pal Pabitra B, Shukla Kirtikar, Ramana Kota V
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Oxid Med Cell Longev. 2017;2017:2769347. doi: 10.1155/2017/2769347. Epub 2017 Jan 24.
Although aspalatone (acetylsalicylic acid maltol ester) is recognized as an antithrombotic agent with antioxidative and antiplatelet potential; its efficacy in preventing endothelial dysfunction is not known. In this study, we examined the antiangiogenic, antioxidative, and anti-inflammatory effect of aspalatone in human aortic endothelial cells (HAECs). Specifically, the effect of aspalatone on VEGF-induced HAECs growth, migration, tube formation, and levels of lipid peroxidation-derived malondialdehyde (MDA) was examined. Our results indicate that the treatment of HAECs with aspalatone decreased VEGF-induced cell migration, tube formation, and levels of MDA. Aspalatone also inhibited VEGF-induced decrease in the expression of eNOS and increase in the expression of iNOS, ICAM-1, and VCAM-1. Aspalatone also prevented the VEGF-induced adhesion of monocytes to endothelial cells. Furthermore, aspalatone also prevented VEGF-induced release of inflammatory markers such as Angiopoietin-2, Leptin, EGF, G-CSF, HB-EGF, and HGF in HAECs. Thus, our results suggest that aspalatone could be used to prevent endothelial dysfunction, an important process in the pathophysiology of cardiovascular diseases.
尽管阿沙帕洛酮(乙酰水杨酸麦芽酚酯)被认为是一种具有抗氧化和抗血小板潜力的抗血栓形成剂,但其在预防内皮功能障碍方面的功效尚不清楚。在本研究中,我们检测了阿沙帕洛酮在人主动脉内皮细胞(HAECs)中的抗血管生成、抗氧化和抗炎作用。具体而言,检测了阿沙帕洛酮对VEGF诱导的HAECs生长、迁移、管腔形成以及脂质过氧化衍生的丙二醛(MDA)水平的影响。我们的结果表明,用阿沙帕洛酮处理HAECs可降低VEGF诱导的细胞迁移、管腔形成以及MDA水平。阿沙帕洛酮还抑制VEGF诱导的eNOS表达降低以及iNOS、ICAM-1和VCAM-1表达增加。阿沙帕洛酮还可防止VEGF诱导的单核细胞与内皮细胞的黏附。此外,阿沙帕洛酮还可防止VEGF诱导的HAECs中炎性标志物如血管生成素-2、瘦素、表皮生长因子、粒细胞集落刺激因子、肝素结合表皮生长因子和肝细胞生长因子的释放。因此,我们的结果表明,阿沙帕洛酮可用于预防内皮功能障碍,这是心血管疾病病理生理学中的一个重要过程。