Mechanisms and pathways of anti-inflammatory activity of DPP-4 inhibitors in cardiovascular and renal protection

Med Res Rev. 2019 Jan;39(1):404-422. doi: 10.1002/med.21513. Epub 2018 May 28.

Abstract

Dipeptidyl peptidase-4 (DPP-4) cleaves N-terminal dipeptides, with Pro, Ala or Ser at the penultimate position, and, in that way, modulates biological activity of certain polypeptides. Due to its ubiquitous distribution, many pathological processes are associated with altered DPP-4 expression and activity. Besides the regulation of glucose metabolism, DPP-4 also exhibits many other systemic effects, and the inhibition of its activity might lead to cardiovascular and renal protection. Mechanisms underlying these protective effects of DPP-4 inhibition are ascribed to elevated bioavailability of its substrates, to impacts on mediators and signaling pathways that ameliorate cardiovascular and renal function through the suppression of oxidative stress, inflammation, fibrosis and apoptosis, improved endothelial function and tissue reparation. Inflammation contributes to and promotes progression of cardiovascular and renal disorders. Herein, we discuss cellular and molecular mechanisms mediating the anti-inflammatory activity of clinically used DPP-4 inhibitors in cardiovascular and renal protection.

Keywords: cardiovascular protection; dipeptidyl peptidase-4 inhibitor; inflammation; renoprotection.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Cardiovascular Diseases / drug therapy*
  • Dipeptidyl Peptidase 4 / metabolism
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Humans
  • Inflammation / pathology
  • Kidney Diseases / drug therapy*

Substances

  • Anti-Inflammatory Agents
  • Dipeptidyl-Peptidase IV Inhibitors
  • Dipeptidyl Peptidase 4