Inhibition of dipeptidyl peptidase 4 regulates microvascular endothelial growth induced by inflammatory cytokines

Biochem Biophys Res Commun. 2010 Oct 8;401(1):7-12. doi: 10.1016/j.bbrc.2010.08.112. Epub 2010 Sep 7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aorta / cytology
  • Aorta / enzymology
  • Cell Proliferation*
  • Collagen
  • Diabetic Angiopathies / drug therapy
  • Diabetic Angiopathies / enzymology
  • Diabetic Angiopathies / pathology
  • Dipeptidyl Peptidase 4 / genetics
  • Dipeptidyl Peptidase 4 / physiology
  • Drug Combinations
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / physiology*
  • Humans
  • Inflammation / enzymology
  • Inflammation / immunology
  • Inflammation / pathology
  • Interleukin-1beta / pharmacology
  • Interleukin-1beta / physiology*
  • Laminin
  • Microvessels / cytology
  • Microvessels / enzymology
  • Microvessels / growth & development
  • Proteoglycans
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tumor Necrosis Factor-alpha / physiology*

Substances

  • Drug Combinations
  • Interleukin-1beta
  • Laminin
  • Proteoglycans
  • Tumor Necrosis Factor-alpha
  • matrigel
  • Collagen
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4