Role of endothelial progenitor cells and inflammatory cytokines in healing of diabetic foot ulcers.

Role of endothelial progenitor cells and inflammatory cytokines in healing of diabetic foot ulcers.
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DOI:
10.1371/journal.pone.0083314
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Veves A
Veves A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Tecilazich F;Dinh T;Pradhan-Nabzdyk L;Leal E;Tellechea A;Kafanas A;Gnardellis C;Magargee ML;Dejam A;Toxavidis V;Tigges JC;Carvalho E;Lyons TE;Veves A

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评估糖尿病足溃疡(DFU)患者内皮祖细胞(EPCs)和细胞因子的变化与伤口愈合的关系。我们研究了健康受试者、无DFU风险的糖尿病患者、有DFU风险的糖尿病患者和活动性DFU患者。我们对DFU患者进行了为期12周的前瞻性随访。我们还研究了糖尿病兔和小鼠伤口愈合模型的类似变化。与对照组相比,除激酶插入结构域受体(KDR)+CD133+外,风险组和DFU组的所有EPC表型均降低。对照组和无风险组之间,风险组和DFU组之间没有主要的EPC差异。DFU患者血清基质细胞衍生因子-1 (SDF-1)和干细胞因子(SCF)升高。溃疡愈合的DFU患者在第3次和第4次就诊时CD34+KDR+计数较低,第1次就诊时血清c反应蛋白(CRP)和粒细胞-巨噬细胞集落刺激因子(GM-CSF)较低,第1次和第4次就诊时白细胞介素-1 (IL-1)较低。与非糖尿病动物模型相比,两种糖尿病动物模型的EPCs在受伤前和10天后都趋于较高。无并发症的糖尿病不影响内皮祖细胞。风险患者或DFU患者EPCs减少,而伤口完全愈合与CD34+KDR+减少相关,提示可能增加归巢。低基线CRP、IL-1α和GM-CSF血清水平与伤口完全愈合相关,可能作为DFU愈合的预后指标。没有一个单独的动物模型能代表人类的情况,这表明需要多种实验模型。
To evaluate changes in endothelial progenitor cells (EPCs) and cytokines in patients with diabetic foot ulceration (DFU) in association with wound healing. We studied healthy subjects, diabetic patients not at risk of DFU, at risk of DFU and with active DFU. We prospectively followed the DFU patients over a 12-week period. We also investigated similar changes in diabetic rabbit and mouse models of wound healing. All EPC phenotypes except the kinase insert domain receptor (KDR)+CD133+ were reduced in the at risk and the DFU groups compared to the controls. There were no major EPC differences between the control and not at risk group, and between the at risk and DFU groups. Serum stromal-cell derived factor-1 (SDF-1) and stem cell factor (SCF) were increased in DFU patients. DFU patients who healed their ulcers had lower CD34+KDR+ count at visits 3 and 4, serum c-reactive protein (CRP) and granulocyte-macrophage colony-stimulating factor (GM-CSF) at visit 1, interleukin-1 (IL-1) at visits 1 and 4. EPCs tended to be higher in both diabetic animal models when compared to their non-diabetic counterparts both before and ten days after wounding. Uncomplicated diabetes does not affect EPCs. EPCs are reduced in patients at risk or with DFU while complete wound healing is associated with CD34+KDR+ reduction, suggesting possible increased homing. Low baseline CRP, IL-1α and GM-CSF serum levels were associated with complete wound healing and may potentially serve as prognostic markers of DFU healing. No animal model alone is representative of the human condition, indicating the need for multiple experimental models.
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