title: Expression and spatial heterogeneity of dipeptidyl peptidases in endothelial cells of conduct vessels and capillaries.
abstract: Dipeptidyl peptidase IV (DPPIV)/CD26 is by far the most extensively studied member of the prolyl oligopeptidase family of serine proteases. The discovery of the related enzymes DPP8 and DPP9 necessitates a (re-)evaluation of the DPPIV-like enzymatic activity in cells and organs. In this study, we aimed (1) to investigate the expression of the individual dipeptidyl peptidases in different types of endothelial cells (ECs) and (2) to reconsider published data in relation to our findings. Examination of DPP expression in rat primary ECs of aortic, endocardial and cardiac microvascular origin revealed the presence of DPPIV-like activity in all cell lysates. More than half of this activity could be attributed to DPP8/9. Western blot analysis revealed an abundance of the DPP8 protein as compared to DPP9. The expression of DPPIV and DPP8 was significantly higher in the cardiac microvascular endothelium than in the other ECs, suggesting a more pronounced role of these DPPs in the microvasculature. In situ, DPP activity in ventricular microvasculature was completely inhibited by sitagliptin, indicating that DPPIV is the predominant DPPIV-like enzyme in this organ. By contrast, immunohistochemical studies indicated DPP9 as the predominant DPP in human carotid artery ECs. In conclusion, our results support a highly regulated expression of individual DPPs in ECs, with a spatial heterogeneity in the cardiovascular tree.
authors.affiliation: Laboratory of Medical Biochemistry, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk (Antwerp), Belgium.
authors.forename: Veerle
authors.initials: V
authors.lastname: Matheeussen
authors.forename: Lesley
authors.initials: L
authors.lastname: Baerts
authors.forename: Guido
authors.initials: G
authors.lastname: De Meyer
authors.forename: Gilles
authors.initials: G
authors.lastname: De Keulenaer
authors.forename: Pieter
authors.initials: P
authors.lastname: Van der Veken
authors.forename: Koen
authors.initials: K
authors.lastname: Augustyns
authors.forename: Véronique
authors.initials: V
authors.lastname: Dubois
authors.forename: Simon
authors.initials: S
authors.lastname: Scharpé
authors.forename: Ingrid
authors.initials: I
authors.lastname: De Meester
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000201:enzymology; D002196:Capillaries / Q000166:cytology; D002339:Carotid Arteries / Q000166:cytology / Q000201:enzymology; D002460:Cell Line; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology*; D006801:Humans; D009206:Myocardium / Q000201:enzymology; D011719:Pyrazines / Q000494:pharmacology; D051381:Rats; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000494:pharmacology
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D011719:Pyrazines; D014230:Triazoles; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C527707:Dpp8 protein, rat; C527708:Dpp9 protein, rat; D018819:Dipeptidyl Peptidase 4; D000068900:Sitagliptin Phosphate