Spliced stromal cell-derived factor-1α analog stimulates endothelial progenitor cell migration and improves cardiac function in a dose-dependent manner after myocardial infarction.
Spliced stromal cell-derived factor-1α analog stimulates endothelial progenitor cell migration and improves cardiac function in a dose-dependent manner after myocardial infarction.
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DOI：
10.1016/j.jtcvs.2010.08.012
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发表时间：
2010-11
影响因子：
6
通讯作者：
Woo, Y. Joseph
中科院分区：
文献类型：
--
作者：
Hiesinger, William;Frederick, John R.;Atluri, Pavan;McCormick, Ryan C.;Marotta, Nicole;Muenzer, Jeffrey R.;Woo, Y. Joseph
基质细胞衍生因子(SDF)-1α是一种有效的内源性内皮祖细胞（EPC）趋化因子和关键的血管生成前体。重组SDF-1α已被证明可以改善心肌梗死（MI）后的新生血管发生和心功能，但SDF-1α是一种半衰期短的大体积蛋白质。小肽类似物可能具有翻译优势，包括易于合成，制造成本低，以及使用工程生物材料控制组织内递送的潜力。我们假设，通过将n端（激活和结合）和c端（细胞外稳定）与截断的氨基酸连接体拼接，设计出一种最小化的SDF-1α肽类似物，可以诱导心肌梗死后EPC迁移并保持心室功能。EPC迁移首先在体外使用Boyden室法测定。为了进行体内分析，雄性大鼠（n=48）接受了左冠状动脉前降支结扎术。梗死后随机分为4组，分别在梗死周心肌内注射生理盐水、3 μg/kg SDF-1α、3 μg/kg剪接SDF类似物、6 μg/kg剪接SDF类似物。4周后，行闭式胸压容积导管分析。EPCs在重组SDF-1α和剪接SDF类似物梯度中均表现出明显的迁移。与对照组大鼠相比，在心肌梗死时接受剪切SDF类似物治疗的大鼠在舒张末压、卒中容积、射血分数、心输出量和卒中功方面表现出明显的剂量依赖性改善。含有天然蛋白N端和C端的SDF-1α的剪接肽类似物诱导EPC迁移，改善急性心肌梗死后的心室功能，与重组人SDF-1α相比，具有翻译优势。
Stromal cell-derived factor (SDF)-1α is a potent endogenous endothelial progenitor cell (EPC) chemokine and key angiogenic precursor. Recombinant SDF-1α has been demonstrated to improve neovasculogenesis and cardiac function after myocardial infarction (MI) but SDF-1α is a bulky protein with a short half-life. Small peptide analogs might provide translational advantages, including ease of synthesis, low manufacturing costs, and the potential to control delivery within tissues using engineered biomaterials. We hypothesized that a minimized peptide analog of SDF-1α, designed by splicing the N-terminus (activation and binding) and C-terminus (extracellular stabilization) with a truncated amino acid linker, would induce EPC migration and preserve ventricular function after MI. EPC migration was first determined in vitro using a Boyden chamber assay. For in vivo analysis, male rats (n=48) underwent left anterior descending coronary artery ligation. At infarction, the rats were randomized into 4 groups and received peri-infarct intramyocardial injections of saline, 3 μg/kg of SDF-1α, 3 μg/kg of spliced SDF analog, or 6 μg/kg spliced SDF analog. After 4 weeks, the rats underwent closed chest pressure volume conductance catheter analysis. EPCs showed significantly increased migration when placed in both a recombinant SDF-1α and spliced SDF analog gradient. The rats treated with spliced SDF analog at MI demonstrated a significant dose-dependent improvement in end-diastolic pressure, stroke volume, ejection fraction, cardiac output, and stroke work compared with the control rats. A spliced peptide analog of SDF-1α containing both the N- and C- termini of the native protein induced EPC migration, improved ventricular function after acute MI, and provided translational advantages compared with recombinant human SDF-1α.
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影响因子：
37.8
作者：
Segers, Vincent F. M.;Tokunou, Tomotake;Lee, Richard T.
通讯作者：
Lee, Richard T.
影响因子：
5.8
作者：
He, Xuezhong;Ma, Junyu;Jabbari, Esmaiel
通讯作者：
Jabbari, Esmaiel
影响因子：
3.4
作者：
Tang, Junming;Wang, Jianing;Huang, Yongzhang
通讯作者：
Huang, Yongzhang
影响因子：
4.6
作者：
Jayasankar, V;Bish, LT;Woo, YJ
通讯作者：
Woo, YJ
影响因子：
168.9
作者：
Askari, AT;Unzek, S;Penn, MS
通讯作者：
Penn, MS