Inhibition of dipeptidyl peptidase 4 regulates microvascular endothelial growth induced by inflammatory cytokines.
Inhibition of dipeptidyl peptidase 4 regulates microvascular endothelial growth induced by inflammatory cytokines.
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DOI：
10.1016/j.bbrc.2010.08.112
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发表时间：
2010-10
影响因子：
3.1
通讯作者：
Wataru Takasawa;K. Ohnuma;R. Hatano;Y. Endo;N. Dang;C. Morimoto
中科院分区：
文献类型：
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作者：
Wataru Takasawa;K. Ohnuma;R. Hatano;Y. Endo;N. Dang;C. Morimoto
CD26/DPP-4在炎性病变的毛细血管和效应性T细胞上大量表达。近年来，抑制CD26/DPP-4已成为治疗2型糖尿病的一种新的口服治疗方法。虽然越来越多的数据表明，血管炎症是糖尿病微血管和大血管并发症的关键特征，但CD26/DPP-4在内皮生物学中的直接作用仍有待阐明。在此，我们发现促炎细胞因子如肿瘤坏死因子或白介素1减少微血管内皮细胞CD26的表达，而CD26/DPP-4的遗传或药物抑制在体外和体内都促进了内皮细胞的生长。随着DPP-4抑制剂在2型糖尿病治疗中的广泛应用，我们的数据有力地表明，DPP-4抑制在内皮细胞生长中起着关键作用，并可能在糖尿病血管并发症后局部循环的恢复中发挥潜在作用。
CD26/DPP-4 is abundantly expressed on capillary of inflamed lesion as well as effector T cells. Recently, CD26/dipeptidyl peptidase 4 (DPP-4) inhibition has been used as a novel oral therapeutic approach for patients with type 2 diabetes. While accumulating data indicate that vascular inflammation is a key feature of both micro- and macro-vascular complications in diabetes, the direct role of CD26/DPP-4 in endothelial biology is to be elucidated. We herein showed that proinflammatory cytokines such as tumor necrosis factor or interleukin-1 reduce expression of CD26 on microvascular endothelial cells, and that genetical or pharmacological inhibition of CD26/DPP-4 enhances endothelial growth both in vitro and in vivo. With DPP-4 inhibitors being used widely in the treatment of type 2 diabetes, our data strongly suggest that DPP-4 inhibition plays a pivotal role in endothelial growth and may have a potential role in the recovery of local circulation following diabetic vascular complications.