Efficacy of fragmin/protamine microparticles containing fibroblast growth factor-2 (F/P MPs/FGF-2) to induce collateral vessels in a rabbit model of hindlimb ischemia
Efficacy of fragmin/protamine microparticles containing fibroblast growth factor-2 (F/P MPs/FGF-2) to induce collateral vessels in a rabbit model of hindlimb ischemia
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DOI：
10.1016/j.jvs.2011.02.060
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发表时间：
2011-09-01
影响因子：
4.3
通讯作者：
Maehara, Tadaaki
中科院分区：
文献类型：
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作者：
Horio, Takuya;Fujita, Masanori;Maehara, Tadaaki
目的：外源性血管生成生长因子如成纤维细胞生长因子（FGF）-2的局部递送已成为外周动脉疾病（PAD）和严重肢体缺血（CLI）的有希望的替代治疗。本研究描述了含FGF-2的法格明/鱼精蛋白微粒（F/P-MPs/FGF-2）促进兔后肢缺血模型血管生长的功效。方法：共24只家兔通过切除左股动脉建立后肢缺血模型。手术后10天（第0天）随机分为4组：A组：对照组（未处理; 1 mL磷酸盐缓冲盐水[PBS]）; B组：FGF-2（100 μ g FGF-2溶于1 mL PBS）处理; C组：F/P-MP D组：F/PMP/FGF-2（100 μ g FGF-2和12 mg干燥F/PMP于1 mL PBS中）-处理（每组n = 6）。各组均经肌肉注射给药。在第0、14和28天测量各组的血流量和血压。在第28天进行血管造影以评估动脉生成。第28天通过直接计数CD 31（-）和is-smooth muscle antibody（α-SMA）阳性血管来确定毛细血管的数量。与对照组、FGF-2治疗组和F/P MP治疗组相比，F/P MP/FGF-2治疗组显示出血流比、血压比和毛细血管数的显著改善。F/P MPs-treated group showed intermediate improvement in blood flow ratio and capillary number in comparison to control groups and FGF-2-treated group.Conclusions：F/P MPs/FGF-2-treated group强烈诱导兔后肢缺血模型中的功能性侧支血管，表明PAD的可能治疗。（J Vasc Surg 2011;54：791-8.）临床相关性。动脉粥样硬化性血管疾病引起的PAD是一个主要的健康问题。尽管最近在外科和放射血管技术方面取得了进展，但某些CLI患者不适合血运重建。已经尝试了各种策略来促进侧支血管的发育。F/P MP可作为FGF-2控释的载体。本研究的目的是评估F/P MPs/FGF-2在兔后肢缺血模型中诱导功能性侧支血管的功效。本研究将为临床上治疗PAD患者提供一种有效的治疗策略。
Objectives: The localized delivery of exogenous, angiogenic growth factors such as fibroblast growth factor (FGF)-2 has become a promising alternative treatment of peripheral artery disease (PAD) and critical limb ischemia (CLI). The present study describes the efficacy of fragmin/protamine microparticles containing FGF-2 (F/P-MPs/FGF-2) to promote vessel growth in a rabbit model of hindlimb ischemia.Methods:A total of 24 rabbits were used to construct a model of hindlimb ischemia by resection of the left femoral artery. The rabbits were randomly divided into four groups 10 days after surgery (day 0); group A: control (non-treated; 1 mL of phosphate-buffered saline [PBS]); group B: FGF-2 (100 mu g FGF-2 in 1 mL PBS)-treated; group C: F/P-MPs (12 mg dried F/P MPs in 1 mL PBS)-treated; and group D; F/P MPs/FGF-2 (100 jig FGF-2 and 12 mg dried F/P MPs in 1 mL PBS)-treated (n = 6 each). The drugs were administered intramuscularly to each group. Blood flow and blood pressure were measured in each group on days 0, 14, and 28. Angiography was performed to assess arteriogenesis on day 28. The number of capillaries on day 28 was determined by direct counting CD31(-) and is-smooth muscle antibody (alpha-SMA)-positive vessels.Results: Neither death nor wound infection was observed throughout the experiment. The F/P MPs/FGF-2-treated group showed marked improvement in the blood flow ratio, blood pressure ratio, and capillary number in comparison to the control group, FGF-2-treated group, and F/P MPs-treated group. The F/P MPs-treated group showed intermediate improvement in blood flow ratio and capillary number in comparison to the control group and FGF-2-treated group.Conclusions: The F/P MPs/FGF-2-treated group strongly induced functional collateral vessels in the rabbit model of hindlimb ischemia, indicating a possible therapy for PAD. (J Vasc Surg 2011;54:791-8.)Clinical Relevance. PAD due to atherosclerotic vascular disease is a major health problem. Despite recent advances in surgical and radiologic vascular techniques, certain patients with CLI are not suitable for revascularization. A variety of strategies have been tried to promote development of collateral vessels. F/P MPs can act as carriers for controlled release of FGF-2. The purpose of this study was to evaluate the efficacy of F/P MPs/FGF-2 to induce functional collateral vessels in a rabbit model of hindlimb ischemia. This study will lead to F/P MPs/FGF-2-therapy which is an effective therapeutic strategy for treating PAD patients in clinic.