Biochemically engineered stromal cell-derived factor 1-alpha analog increases perfusion in the ischemic hind limb
Biochemically engineered stromal cell-derived factor 1-alpha analog increases perfusion in the ischemic hind limb
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DOI：
10.1016/j.jvs.2015.06.140
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发表时间：
2016-10-01
影响因子：
4.3
通讯作者：
Woo, Y. Joseph
中科院分区：
文献类型：
--
作者：
Edwards, Bryan B.;Fairman, Alexander S.;Woo, Y. Joseph
背景资料：尽管在过去的十年中有希望的治疗创新，外周动脉疾病仍然是一种普遍的发病率，因为许多患者仍然面临外周缺血的挑战。我们假设在缺血后肢中递送工程化基质细胞衍生因子1-α（ESA）将显着改善灌注。方法：雄性大鼠接受右股动脉结扎，动物随机接受100 μ L注射盐水（n = 9）或6 μ g/kg剂量的等体积ESA（n = 12）进入同侧股四头肌。两组动物均腹腔注射40 μ g/kg粒细胞巨噬细胞集落刺激因子（GMCSF）。在术前、术后第0、7和14天，使用激光多普勒成像设备对灌注进行定量。结果：与生理盐水/GMCSF组相比，ESA/GMCSF组动物在第14天有更高的再灌注率（生理盐水/GMCSF，0.600 +/- 0.140 vs ESA/GMCSF，0.900 +/- 0.181;组效应P = .006;时间效应P < .0001;组×时间效应P < .0001），毛细血管密度升高（103;生理盐水/GMCSF，6.40 +/- 2.01 vs ESA/GMCSF，18.55 +/- 5.30; P < .01），并增加血管内皮生长因子-A的mRNA水平（生理盐水/GMCSF [n = 6]，0.298 +/- 0.205 vs ESA/GMCSF [n = 8]，0.456 +/- 0.139; P = 0.03）。ESA的递送通过改善的新血管生成显著改善外周动脉疾病大鼠模型中的灌注，这一发现可能证明对这种使人衰弱的疾病的治疗策略有益。
Background: Despite promising therapeutic innovation over the last decade, peripheral arterial disease remains a prevalent morbidity, as many patients are still challenged with peripheral ischemia. We hypothesized that delivery of engineered stromal cell-derived factor 1-alpha (ESA) in an ischemic hind limb will yield significant improvement in perfusion.Methods: Male rats underwent right femoral artery ligation, and animals were randomized to receive a 100 mu L injection of saline (n = 9) or 6 mu g/kg dosage of equal volume of ESA (n = 12) into the ipsilateral quadriceps muscle. Both groups of animals were also given an intraperitoneal injection of 40 mu g/kg of granulocyte macrophage colony-stimulating factor (GMCSF). Perfusion was quantified using a laser Doppler imaging device preoperatively, and on postoperative days 0, 7, and 14. Immunohistochemistry was performed to quantify angiogenesis on day 14, and an mRNA profile was evaluated for angiogenic and inflammatory markers.Results: Compared with the saline/GMCSF group at day 14, the ESA/GMCSF-injected animals had greater reperfusion ratios (Saline/GMCSF, 0.600 +/- 0.140 vs ESA/GMCSF, 0.900 +/- 0.181; group effect P = .006; time effect P < .0001; groupxtime effect P < .0001), elevated capillary density (103; Saline/GMCSF, 6.40 +/- 2.01 vs ESA/GMCSF, 18.55 +/- 5.30; P < .01), and increased mRNA levels of vascular endothelial growth factor-A (Saline/GMCSF [n = 6], 0.298 +/- 0.205 vs ESA/GMCSF [n = 8], 0.456 +/- 0.139; P = .03).Conclusions: Delivery of ESA significantly improves perfusion in a rat model of peripheral arterial disease via improved neovasculogenesis, a finding which may prove beneficial in the treatment strategy for this debilitating disease.