Defective CXCR4 expression in aged bone marrow cells impairs vascular regeneration.
Defective CXCR4 expression in aged bone marrow cells impairs vascular regeneration.
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DOI：
10.1111/j.1582-4934.2010.01231.x
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发表时间：
2011-10
影响因子：
5.3
通讯作者：
Yu H
中科院分区：
文献类型：
--
作者：
Shao H;Xu Q;Wu Q;Ma Q;Salgueiro L;Wang J;Eton D;Webster KA;Yu H
趋化因子基质细胞衍生因子-1（SDF-1）在动员骨髓中的前体细胞方面起着关键作用，并且对于有效的血管再生和修复至关重要。我们最近报道了钙增加趋化因子受体CXCR 4的表达并增强骨髓源性细胞（BMCs）的血管生成潜能。新血管形成受到衰老的损害，因此我们认为衰老可能导致CXCR 4表达和细胞对钙反应的缺陷。事实上，我们发现，与2个月大的小鼠相比，25个月大的小鼠的BMCs上CXCR 4的基础和钙诱导的表面表达显著降低。老年小鼠BMC中钙诱导的CXCR 4表达减少与钙内流缺陷有关。老年小鼠BMC中CXCR 4表面表达减少与缺血后肢模型中新生血管减少相关，缺血肌肉中CD 34+祖细胞积聚较少，伴或不伴SDF-1局部过表达。与年轻小鼠的骨髓细胞相比，静脉注射老年小鼠的骨髓细胞对缺血肌肉的归巢效率较低，刺激的新血管形成明显较少。将旧的BMCs移植到年轻的小鼠中并不能重建CXCR 4的功能，这表明这种缺陷是不能通过改变环境来逆转的。我们的结论是，BMCs中CXCR 4/SDF-1轴的基础和钙调节功能的缺陷显著导致与年龄相关的血管生成反应的丧失。
The chemokine stromal cell-derived factor-1 (SDF-1) plays a critical role in mobilizing precursor cells in the bone marrow and is essential for efficient vascular regeneration and repair. We recently reported that calcium augments the expression of chemokine receptor CXCR4 and enhances the angiogenic potential of bone marrow derived cells (BMCs). Neovascularization is impaired by aging therefore we suggested that aging may cause defects of CXCR4 expression and cellular responses to calcium. Indeed we found that both the basal and calcium-induced surface expression of CXCR4 on BMCs was significantly reduced in 25-month-old mice compared with 2-month-old mice. Reduced Ca-induced CXCR4 expression in BMC from aged mice was associated with defective calcium influx. Diminished CXCR4 surface expression in BMC from aged mice correlated with diminished neovascularization in an ischemic hindlimb model with less accumulation of CD34+ progenitor cells in the ischemic muscle with or without local overexpression of SDF-1. Intravenous injection of BMCs from old mice homed less efficiently to ischemic muscle and stimulated significantly less neovascularization compared with the BMCs from young mice. Transplantation of old BMCs into young mice did not reconstitute CXCR4 functions suggesting that the defects were not reversible by changing the environment. We conclude that defects of basal and calcium-regulated functions of the CXCR4/SDF-1 axis in BMCs contribute significantly to the age-related loss of vasculogenic responses.
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DOI：
10.1084/jem.184.2.569
发表时间：
1996-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Loetscher P;Seitz M;Baggiolini M;Moser B
通讯作者：
Moser B
影响因子：
24
作者：
Heiss, C;Keymel, S;Kalka, C
通讯作者：
Kalka, C
影响因子：
20.3
作者：
Eash, Kyle J.;Means, Jacquelyn M.;Link, Daniel C.
通讯作者：
Link, Daniel C.
影响因子：
4.8
作者：
Helbig, G;Christopherson, KW;Nakshatri, H
通讯作者：
Nakshatri, H
影响因子：
7.7
作者：
Loomans, CJM;de Koning, EJP;van Zonneveld, AJ
通讯作者：
van Zonneveld, AJ