Hoenig Michel R, Bianchi Cesario, Rosenzweig Anthony, Sellke Frank W
Center for Clinical Research, Building 71, Royal Brisbane & Women's Hospital, Herston Qld 4029, Australia.
Curr Mol Med. 2008 Dec;8(8):754-67. doi: 10.2174/156652408786733685.
Ageing is associated with endothelial dysfunction, decreased endothelial progenitor cell (EPC) function and mobilization. These defects culminate in a decreased capacity for neovascularization in the aged. Multiple lines of evidence suggest that defective neovascularization with ageing is related to depressed signaling by hypoxia inducible factor-1 (HIF-1). HIF-1, the master regulator or neovascularization, regulates the expression of vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 (SDF-1) and CXC chemokine Receptor-4 (CXCR4). Given that the SDF-1/CXCR4 axis is a crucial regulator of progenitor cell function and homing, the ramifications of depressed HIF-1 signaling with age include depressed vascular repair, neovascularization and wound healing. We review the literature showing the depression of these processes with age and discuss the relevance of these findings to several clinical contexts. Further, the effects of age on EPC number, function and mobilization are related to the age-related decline in HIF-1 signaling. We suggest that exercise, Cobalt compounds or hydralazine may reverse the age-related decline by up-regulating HIF-1-mediated signaling.
衰老与内皮功能障碍、内皮祖细胞（EPC）功能及动员能力下降相关。这些缺陷最终导致老年人血管新生能力降低。多条证据表明，衰老导致的血管新生缺陷与缺氧诱导因子-1（HIF-1）信号传导受抑制有关。HIF-1是血管新生的主要调节因子，可调节血管内皮生长因子（VEGF）、基质细胞衍生因子-1（SDF-1）和CXC趋化因子受体4（CXCR4）的表达。鉴于SDF-1/CXCR4轴是祖细胞功能和归巢的关键调节因子，衰老导致的HIF-1信号传导受抑制的后果包括血管修复、血管新生及伤口愈合能力下降。我们回顾了显示这些过程随年龄增长而受抑制的文献，并讨论了这些发现与几种临床情况的相关性。此外，年龄对EPC数量、功能及动员的影响与HIF-1信号传导随年龄增长而下降有关。我们认为，运动、钴化合物或肼屈嗪可能通过上调HIF-1介导的信号传导来逆转与年龄相关的下降。
