Analysis of CD45-[CD34+/KDR+] Endothelial Progenitor Cells as Juvenile Protective Factors in a Rat Model of Ischemic-Hemorrhagic Stroke
Analysis of CD45-[CD34+/KDR+] Endothelial Progenitor Cells as Juvenile Protective Factors in a Rat Model of Ischemic-Hemorrhagic Stroke
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DOI：
10.1371/journal.pone.0055222
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发表时间：
2013-01-31
期刊：
影响因子：
3.7
通讯作者：
Herrera, Victoria L. M.
中科院分区：
文献类型：
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作者：
Decano, Julius L.;Moran, Ann Marie;Herrera, Victoria L. M.
背景：识别随年龄变化的青少年保护因子(JPF)有助于逆转年龄的影响，而年龄是成人发病的不可改变的危险因素。由于在中风、高血压和高胆固醇血症中观察到内皮祖细胞(EPC)的改变，因此EPC是成人起病卒中的候选JPF。根据先验，如果EPC老化在卒中发病机制中起“主开关JPF作用”，那么单靠青少年EPC治疗就应该延缓卒中的发病。利用高血压转基因高脂血症自发性脑缺血-出血性卒中大鼠模型spTg25，我们验证了这一假说，即新鲜分离的幼年内皮祖细胞是能够延缓卒中进展和延迟卒中发病的JPF。方法/主要发现：FACS分析显示，在spTg25大鼠中，CD45-[CD34+/KDR+]内皮祖细胞随着卒中的进展而减少，表现出双重内毒素-1/VEGFSP受体(Despr)的差异表达，并在数量和体外血管生成管掺入方面经历了不同Despr亚型的特异性变化。在体内，雌性卒中易感大鼠体内输注雄性、幼年未扩张的CD45-[CD34+/KDR+]EPC可缓解迟发性卒中(P
Background: Identification of juvenile protective factors (JPFs) which are altered with age and contribute to adult-onset diseases could identify novel pathways for reversing the effects of age, an accepted non-modifiable risk factor to adult-onset diseases. Since endothelial progenitor cells (EPCs) have been observed to be altered in stroke, hypertension and hypercholesterolemia, said EPCs are candidate JPFs for adult-onset stroke. A priori, if EPC aging plays a 'master-switch JPF-role' in stroke pathogenesis, juvenile EPC therapy alone should delay stroke-onset. Using a hypertensive, transgenic-hyperlipidemic rat model of spontaneous ischemic-hemorrhagic stroke, spTg25, we tested the hypothesis that freshly isolated juvenile EPCs are JPFs that can attenuate stroke progression and delay stroke onset.Methodology/Principal Findings: FACS analysis revealed that CD45- [CD34+/KDR+] EPCs decrease with progression to stroke in spTg25 rats, exhibit differential expression of the dual endodthelin-1/VEGFsp receptor (DEspR) and undergo differential DEspR-subtype specific changes in number and in vitro angiogenic tube-incorporation. In vivo EPC infusion of male, juvenile non-expanded CD45-[CD34+/KDR+] EPCs into female stroke-prone rats prior to stroke attenuated delayed stroke onset (P