Age-Related Decline in Reendothelialization Capacity of Human Endothelial Progenitor Cells Is Restored by Shear Stress
Age-Related Decline in Reendothelialization Capacity of Human Endothelial Progenitor Cells Is Restored by Shear Stress
复制标题
人内皮祖细胞与年龄相关的再内皮化能力下降可通过剪切应力恢复
DOI：
10.1161/hypertensionaha.111.179820
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发表时间：
2012-06-01
期刊：
影响因子：
8.3
通讯作者：
Tao, Jun
中科院分区：
文献类型：
--
作者：
Xia, Wen Hao;Yang, Zhen;Tao, Jun
衰老与内皮祖细胞（EPCs）功能障碍有关，而切应力对EPCs功能有有益影响;然而，衰老和切应力对动脉损伤后EPCs内皮修复能力的影响尚未见报道。本研究旨在探讨衰老和切应力对人内皮祖细胞再内皮化能力的影响及其分子机制。与年轻人EPCs相比，老年人EPCs在体外迁移和粘附能力降低，移植到颈动脉剥脱损伤裸鼠体内后，其再内皮化能力明显降低。剪切应力预处理增强了年轻和老年EPCs的迁移、粘附和再内皮化能力;然而，在老年EPCs中的作用更大。虽然基础CXC趋化因子受体4（CXCR 4）的表达是相似的EPCs从2个年龄组，基质细胞衍生因子1诱导的CXCR 4和Janus激酶2磷酸化在老年人比年轻的EPCs低得多。剪切应力处理上调CXCR 4的表达和磷酸化，重要的是，恢复了老年EPCs中基质细胞衍生因子1/CXCR 4依赖性Janus激酶2的磷酸化。此外，短发夹RNA介导的CXCR 4表达的敲低或用Janus激酶2抑制剂预处理减少了剪切应力处理对老年EPCs迁移、粘附和再内皮化能力的增强。因此，我们的研究表明，上调CXCR 4/Janus激酶2途径的剪切应力有助于增强内皮祖细胞的再内皮化能力，从老年男性。（高血压。2012; 59：1225-1231）。在线补充资料
Aging is associated with dysfunction of endothelial progenitor cells (EPCs), and shear stress has a beneficial impact on EPC function; however, the effects of aging and shear stress on the endothelial repair capacity of EPCs after arterial injury have not been reported. Here we investigated the influence of aging and shear stress on the reendothelialization capacity of human EPCs and the related molecular mechanism. Compared with EPCs isolated from young subjects, EPCs from the elderly displayed an impaired migration and adhesion in vitro and demonstrated a significantly reduced reendothelialization capacity in vivo after transplantation into nude mice with carotid artery denudation injury. Shear stress pretreatment enhances the migration, adhesion, and reendothelialization capacity in both young and elderly EPCs; however, it was to a greater extent in EPCs from the elderly. Although basal CXC chemokine receptor 4 (CXCR4) expression was similar in EPCs from the 2 age groups, the stromal cell derived factor 1-induced CXCR4 and Janus kinase 2 phosphorylations were much lower in the elderly than in young EPCs. Shear stress treatment upregulated CXCR4 expression and phosphorylation and, importantly, restored the stromal cell-derived factor 1/CXCR4-dependent Janus kinase 2 phosphorylation in the elderly EPCs. Furthermore, short hairpin RNA-mediated knockdown of CXCR4 expression or pretreatment with Janus kinase 2 inhibitor diminished the enhancement in the migration, adhesion, and reendothelialization capacity of the elderly EPCs from shear stress treatments. Thus, our study demonstrates that upregulation of the CXCR4/Janus kinase 2 pathway by shear stress contributes to the enhanced reendothelialization capacity of EPCs from elderly men. (Hypertension. 2012; 59: 1225-1231.). Online Data Supplement