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DPP4 Promotes Human Endothelial Cell Senescence and Dysfunction via the PAR2-COX-2-TP Axis and NLRP3 Inflammasome

Inés Valencia1,2,3, Susana Vallejo1,3, Pilar Dongil1,3

  • 1Department of Pharmacology and Therapeutics, School of Medicine (I.V., S.V., P.D., A.R., Á.S.H.-L., L.S., T.R., C.P., C.F.S.-F.), Universidad Autónoma de Madrid, Spain.

Hypertension (Dallas, Tex. : 1979)
|April 28, 2022
PubMed
Abstract

Insights

Soluble DPP4 (dipeptidyl peptidase 4) accelerates vascular aging by promoting endothelial cell senescence and dysfunction. Blocking DPP4 activity restores vascular function, suggesting it as a therapeutic target for age-related vascular decline.

Area of Science:

  • Vascular Biology
  • Cellular Senescence
  • Obesity Research

Background:

  • Vascular aging is linked to senescent cell accumulation in vessel walls.
  • Obesity, a progeric condition, increases soluble DPP4 (dipeptidyl peptidase 4) secretion.
  • The role of sDPP4 in vascular aging and its endothelial mechanisms remain unexplored.

Purpose of the Study:

  • To investigate the involvement of sDPP4 in vascular aging.
  • To elucidate the molecular pathways through which sDPP4 affects the endothelium.

Main Methods:

  • Assessed endothelial cell senescence using senescence markers and DNA damage assays.
  • Evaluated vascular function in human microvessels via myography.
  • Analyzed age-related parameters in visceral adipose tissue from obese patients.

Main Results:

  • sDPP4 induces endothelial senescence and dysfunction via the PAR2-COX-2-TP axis, activating the NLRP3 inflammasome.
  • Obese patients show impaired microarterial function, correlating with elevated DPP4 and pro-inflammatory markers.
  • Inhibition of DPP4 activity or sDPP4-induced senescence reversed endothelial dysfunction.

Conclusions:

  • sDPP4 is a key mediator in early vascular aging.
  • sDPP4 activates pro-inflammatory pathways in the endothelium.
  • Targeting sDPP4 offers a potential therapeutic strategy for vascular aging.
Keywords:
cellular senescencedipeptidyl peptidase 4endotheliuminflammasomesmicrovesselsobesity

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