Inhibition of dipeptidyl peptidase 4 regulates microvascular endothelial growth induced by inflammatory cytokines.
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.
Takasawa
Wataru
W
Division of Clinical Immunology, The Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Ohnuma
Kei
K
Hatano
Ryo
R
Endo
Yuko
Y
Dang
Nam H
NH
Morimoto
Chikao
C
D001011:Aorta / Q000166:cytology / Q000201:enzymology; D049109:Cell Proliferation; D003094:Collagen; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000502:physiology; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D053583:Interleukin-1beta / Q000494:pharmacology / Q000502:physiology*; D007797:Laminin; D055806:Microvessels / Q000166:cytology / Q000201:enzymology / Q000254:growth & development; D011509:Proteoglycans; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*
D004338:Drug Combinations; D053583:Interleukin-1beta; D007797:Laminin; D011509:Proteoglycans; D014409:Tumor Necrosis Factor-alpha; C059485:matrigel; D003094:Collagen; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4