Endothelial progenitor cell dysfunction - A novel concept in the pathogenesis of vascular complications of type 1 diabetes
Endothelial progenitor cell dysfunction - A novel concept in the pathogenesis of vascular complications of type 1 diabetes
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DOI：
10.2337/diabetes.53.1.195
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发表时间：
2004-01-01
期刊：
影响因子：
7.7
通讯作者：
van Zonneveld, AJ
中科院分区：
文献类型：
--
作者：
Loomans, CJM;de Koning, EJP;van Zonneveld, AJ
1型糖尿病与血管修复减少有关，如创面愈合受损和缺血时侧支循环形成减少所示。近年来，内皮祖细胞被认为是这些过程的重要调节因子。因此，我们探讨了内皮祖细胞在糖尿病中功能失调的概念。培养中的1型糖尿病患者获得的内皮祖细胞数量比年龄和性别匹配的对照组低44%(P<；0.001)。这种下降与HBA(1c)水平呈负相关(R=-0.68，P=0.01)。此外，我们还通过体外血管生成试验证明了患者内皮祖细胞功能受损。与对照内皮祖细胞相比，患者内皮祖细胞的条件培养液支持内皮管形成的能力显著降低。因此，尽管在正常血糖条件下培养内皮祖细胞，患者和对照内皮祖细胞之间的功能差异仍然存在。我们的研究结果表明，1型糖尿病患者的不良代谢应激因素与EPC数量减少和血管生成有关。我们假设EPC功能障碍与1型糖尿病血管并发症的发病机制有关。
Type 1 diabetes is associated with reduced vascular repair, as indicated by impaired wound healing and reduced collateral formation in ischemia. Recently, endothelial progenitor cells (EPCs) have been identified as important regulators of these processes. We therefore explored the concept that EPCs are dysfunctional in diabetes. The number of EPCs obtained from type 1 diabetic patients in culture was 44% lower compared with age- and sex-matched control subjects (P < 0.001). This reduction was inversely related to levels of HbA(1c) (R = -0.68, P = 0.01). In addition, we demonstrated that patient EPCs were also impaired in function using an in vitro angiogenesis assay. Conditioned media from patient EPCs were significantly reduced in their capacity to support endothelial tube formation in comparison to control EPCs. Therefore, despite culturing the EPCs under normoglycemic conditions, functional differences between patient and control EPCs were maintained. Our findings demonstrate that adverse metabolic stress factors in type 1 diabetes are associated with reduced EPC numbers and angiogenicity. We hypothesize that EPC dysfunction contributes to the pathogenesis of vascular complications in type 1 diabetes.