Stromal Cell-Derived Factor-1 Retention and Cardioprotection for Ischemic Myocardium
Stromal Cell-Derived Factor-1 Retention and Cardioprotection for Ischemic Myocardium
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DOI：
10.1161/circheartfailure.110.960302
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发表时间：
2011-07-01
影响因子：
9.7
通讯作者：
Lee, Richard T.
中科院分区：
文献类型：
--
作者：
Kanki, Sachiko;Segers, Vincent F. M.;Lee, Richard T.
基质细胞衍生因子-1（SDF-1）是干/祖细胞的趋化因子，一些研究表明SDF-1可改善梗死后的心室功能。SDF-1被包括基质金属蛋白酶-2（MMP-2）和CD 26/二肽基肽酶-4（DPP-4）在内的蛋白酶裂解，这些蛋白酶在损伤组织中被激活。方法和结果-我们研究了SDF-1在大鼠实验性缺血/再灌注损伤中的生物分布和功能作用。经冠状动脉内注射放射性标记的SDF-1选择性地集中在缺血心肌。SDF-1在缺血心肌中的摄取增加不是由其受体CXCR 4介导的。质谱和Western分析表明，SDF-1在血浆和心肌中被DPP-4切割，而生物工程的MMP-2/DPP-4抗性形式的SDF-1，SSDF-1（S4 V）是高度稳定的。单剂量的SSDF 1（S4 V）表现出比野生型SDF-1更强的心脏保护效力。SSDF-1（S4 V）改善了大鼠的心脏功能，即使在3小时的缺血periods. Conclusions，这些结果表明，单剂量的抗蛋白酶SSDF-1（S4 V）心肌梗死后导致血管生成和心室功能显着改善，即使3小时后缺血发作，揭示了一个简单的，临床上可行的方法来预防心力衰竭。(Circ心脏衰竭。2011; 4：509-518）。
Background-Stromal cell-derived factor-1 (SDF-1) is a chemoattractant of stem/progenitor cells, and several studies have shown that SDF-1 may improve ventricular function after infarction. SDF-1 is cleaved by proteases including matrix metalloproteinase-2 (MMP-2) and CD26/dipeptidylpeptidase-4 (DPP-4), which are activated in injured tissues.Methods and Results-We investigated the biodistribution and functional roles of SDF-1 in experimental ischemia/reperfusion injury in rats. Radiolabeled SDF-1 given by intracoronary injection was selectively concentrated in ischemic myocardium. The enhanced uptake of SDF-1 in ischemic myocardium was not mediated by its receptor, CXCR4. Mass spectrometry and Western analyses showed that SDF-1 was cleaved by DPP-4 in plasma and myocardium, whereas a bioengineered MMP-2/DPP-4-resistant form of SDF-1, SSDF-1(S4V), was highly stable. A single dose of SSDF1(S4V) exhibited greater potency for cardioprotection than wild-type SDF-1. SSDF-1(S4V) improved cardiac function in rats even after a 3-hour ischemic period.Conclusions-These results show that a single dose of protease-resistant SSDF-1(S4V) after myocardial infarction leads to dramatic improvement in angiogenesis and ventricular function even 3 hours after the onset of ischemia, revealing a simple, clinically feasible approach to prevention of heart failure. (Circ Heart Fail. 2011; 4: 509-518.)