Role of Dipeptidyl Peptidase-4 in Atherosclerotic Cardiovascular Disease in Humans and Animals with Chronic Stress

Int Heart J. 2021 May 29;62(3):470-478. doi: 10.1536/ihj.20-181. Epub 2021 May 15.

Abstract

Exposure to psychosocial stress is a risk factor for cardiovascular disease, including vascular atherosclerosis-based cardiovascular disease (ACVD). Dipeptidyl peptidase-4 (DPP-4) is a complex enzyme that acts as a membrane-anchored cell surface exopeptidase. DPP-4 is upregulated in metabolic and inflammatory cardiovascular disorders. DPP-4 exhibits many physiological and pharmacological functions by regulating its extremely abundant substrates, such as glucagon-like peptide-1 (GLP-1). Over the last 10 years, emerging data have demonstrated unexpected roles of DPP-4 in extracellular and intracellular signaling, immune activation, inflammation, oxidative stress production, cell apoptosis, insulin resistance, and lipid metabolism. This mini-review focuses on recent novel findings in this field, highlighting a DPP-4-mediated regulation of GLP-1-dependent and -independent signaling pathways as a potential therapeutic molecular target in treatments of chronic psychological stress-related ACVD in humans and animals.

Keywords: Atherosclerosis; Inflammation; Oxidative stress; Vascular senescence.

Publication types

  • Review

MeSH terms

  • Animals
  • Atherosclerosis / enzymology*
  • Atherosclerosis / etiology
  • Biomarkers / blood
  • Clinical Trials as Topic
  • Dipeptidyl Peptidase 4 / metabolism*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Glucagon-Like Peptide 1 / blood
  • Humans
  • Molecular Targeted Therapy
  • Stress, Psychological / blood
  • Stress, Psychological / complications
  • Stress, Psychological / enzymology*

Substances

  • Biomarkers
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glucagon-Like Peptide 1
  • Dipeptidyl Peptidase 4