Laboratory of Vascular Biology and Genetics, Department of Medicine, A Gemelli University Hospital, Catholic University School of Medicine, Rome, Italy.
Int J Cardiol. 2013 Aug 10;167(3):910-6. doi: 10.1016/j.ijcard.2012.03.103. Epub 2012 Apr 2.
BACKGROUND/OBJECTIVES: Cilostazol has been found to be effective for the treatment of intermittent claudication (IC). This compound has several beneficial effects on platelet aggregation, serum lipids and endothelial cells, but how these might relate to improvements in walking is not entirely understood. The aim of this work was to investigate the effects of cilostazol on angiogenic response in a murine model of peripheral ischemia and to clarify the underlying molecular mechanisms of that response.
We studied ischemia-induced neovascularization in the ischemic hindlimb of cilostazol-treated and untreated control mice.
We found that the perfusion recovery was significantly improved in treated compared with control mice. Interestingly, there was a higher level of circulating endothelial progenitor cells (EPCs) in mice treated with cilostazol than in untreated mice. Furthermore, cilostazol administration resulted in upregulation of granulocyte colony-stimulating factor (G-CSF) and vascular endothelial growth factor (VEGF) in the ischemic muscle of treated mice. Finally, inhibiting VEGF activity significantly reduced cilostazol-induced angiogenesis.
The results of this study show that cilostazol administration enhances collateral blood flow in the ischemic hindlimbs of mice through a VEGF-dependent mechanism. These data may help to explain the beneficial effects that this drug has on patients with peripheral arterial disease (PAD) and IC.
背景/目的：西洛他唑已被证明对间歇性跛行（IC）的治疗有效。该化合物对血小板聚集、血清脂质和内皮细胞有多种有益作用，但这些作用如何与步行能力的改善相关，目前还不完全清楚。本研究旨在探讨西洛他唑在周围缺血小鼠模型中的血管生成反应中的作用，并阐明该反应的潜在分子机制。
我们研究了西洛他唑治疗和未治疗的对照组小鼠缺血后肢中的缺血诱导性新生血管形成。
我们发现，与对照组相比，治疗组的灌注恢复明显改善。有趣的是，与未治疗的小鼠相比，西洛他唑治疗的小鼠中循环内皮祖细胞（EPCs）水平更高。此外，西洛他唑给药导致治疗小鼠缺血肌肉中粒细胞集落刺激因子（G-CSF）和血管内皮生长因子（VEGF）的上调。最后，抑制 VEGF 活性显著降低了西洛他唑诱导的血管生成。
本研究结果表明，西洛他唑给药通过 VEGF 依赖性机制增强了缺血后肢的侧支血流。这些数据可能有助于解释该药物对周围动脉疾病（PAD）和 IC 患者的有益作用。
