Endothelial Progenitor Cells (EPCs) Mobilized and Activated by Neurotrophic Factors May Contribute to Pathologic Neovascularization in Diabetic Retinopathy
Endothelial Progenitor Cells (EPCs) Mobilized and Activated by Neurotrophic Factors May Contribute to Pathologic Neovascularization in Diabetic Retinopathy
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神经营养因子动员和激活的内皮祖细胞 (EPC) 可能有助于糖尿病视网膜病变的病理性新生血管形成
DOI：
10.2353/ajpath.2010.081152
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发表时间：
2010-01-01
影响因子：
6
通讯作者：
Goldschmidt-Clermont, Pascal J.
中科院分区：
文献类型：
--
作者：
Liu, Xialin;Li, Yongjun;Goldschmidt-Clermont, Pascal J.
糖尿病视网膜病变的特征在于病理性视网膜新生血管形成。越来越多的证据表明，高水平的循环内皮祖细胞（EPCs）是新生血管形成的重要危险因素。巧合的是，循环EPCs的减少和功能障碍在糖尿病患者中已被广泛报道。我们假设EPCs在糖尿病的各种血管病变并发症中发生了差异性改变，在对缺血和生长因子的血管生成反应方面表现出不同的行为，并可能在激发血管前体诱导病理性新血管形成方面发挥重要作用。通过流式细胞术和EPC集落形成单位计数分析糖尿病视网膜病变患者的循环EPC水平，并通过酶联免疫吸附试验测定血清神经营养因子水平。我们发现糖尿病视网膜病变患者血液中神经生长因子和脑源性神经营养因子水平升高;这种升高与循环EPCs水平相关。此外，我们证明了视网膜细胞在缺氧条件下释放神经营养因子，以增强体外EPC活性，并增加小鼠缺血后肢模型中的血管生成。这些结果提示，神经营养因子可能通过激活EPC诱导新生血管形成，导致病理性视网膜新生血管形成。因此，我们认为缺血性视网膜新生血管的形成可能受到神经营养因子过度表达的调控。(Am J Pathol 2010，176：504-515; DOI：10.2353/ajpath.2010.081152）
Diabetic retinopathy is characterized by pathological retinal neovascularization. Accumulating evidence has indicated that high levels of circulating endothelial progenitor cells (EPCs) are an important risk factor for neovascularization. Paradoxically, the reduction and dysfunction of circulating EPCs has been extensively reported in diabetic patients. We hypothesized that EPCs are differentially altered in the various vasculopathic complications of diabetes mellitus, exhibiting distinct behaviors in terms of angiogenic response to ischemia and growth factors and potentially playing a potent role in motivating vascular precursors to induce pathological neovascularization. Circulating levels of EPCs from diabetic retinopathy patients were analyzed by flow cytometry and by counting EPC colony-forming units, and serum levels of neurotrophic factors were measured by enzyme-linked immunosorbent assay. We found increased levels of nerve growth factor and brain-derived neurotrophic factor in the blood of diabetic retinopathy patients; this increase was correlated with the levels of circulating EPCs. In addition, we demonstrated that retinal cells released neurotrophic factors under hypoxic conditions to enhance EPC activity in vitro and to increase angiogenesis in a mouse ischemic hindlimb model. These results suggest that neurotrophic factors may induce neoangiogenesis through EPC activation, leading to the pathological retinal neovascularization. Thus, we propose that neovascularization in the ischemic retina might be regulated by overexpression of neurotrophic factors. (Am J Pathol 2010, 176:504-515; DOI: 10.2353/ajpath.2010.081152)