A potential contribution of dipeptidyl peptidase-4 by the mediation of monocyte differentiation in the development and progression of abdominal aortic aneurysms

Abstract

Increased plasma DPP-4 activity may correlate with aneurysmal development. CD26 on monocytes plays a critical role in cell differentiation, possibly mediated by extracellular signal-regulated protein kinase 1/2-p21 axis signaling pathways and cytoskeletal proteins reassembly. Exploring the role of DPP-4 further may yield potential therapeutic insights.

Dipeptidyl peptidase-4 is increased in the abdominal aortic aneurysm vessel wall and is associated with aneurysm disease processes

“…Krizhanovskii et al showed increased GLP1 in plasma of patients with dilatation of the ascending aorta, which could imply a decreased DPP-4 activity, and other studies have found a decreased DPP-4 activity in the plasma of patients with chronic obstructive pulmonary disease, a disease that has been linked to AAA rupture [40][41][42]. However, Lu et al detected a significant increase in DPP-4 in plasma from patients with AAA compared with the control group [16]. This discrepancy cannot be fully explained but our groups of study subjects differ, where Lu et al had a younger group of controls compared to the AAA patients.…”

“…Interestingly, favourable effects of both DPP4 inhibition and GLP-1 on AAA development and progression have been reported for animal models [13][14][15][16][17][18]. However, there are no reports showing the expression and activity of DPP4 in human aneurysm tissue.…”

Diabetes mellitus and abdominal aortic aneurysms: A review of the mechanisms underlying the negative relationship

“…58 DPP4 inhibitors work by augmenting the incretin effect. Lu et al 59 have shown a positive correlation between the relative intensity of plasma DPP4 and AAA diameter (p < 0.05) which may be mediated through an action of DPP4 on monocyte-macrophage differentiation. Using the DPP4 inhibitor alogliptin, Bao et al were able to attenuate aneurysm formation in a dose-dependent fashion (p < 0.02) using rodent models of AAA (intraluminal elastase and extraluminal calcium chloride).…”

“…Furthermore, they found that alogliptin treatment was associated with lower tissue levels of MMP-2 (p < 0.001), MMP-9 (p < 0.001) and reactive oxygen species (p < 0.0001) and preservation of mural elastin. 59 Kohashi et al 60 performed a similar study using the DPP inhibitor MK0626 in an ApoE-deficient AngII mouse model and found that treatment with MK0626, but not treatment with native incretins GIP-1 or GLP-1, was associated with a 30% reduction in aneurysm formation, significantly less IL-1β expression and an increased ratio of tissue inhibitor of metalloproteinase (TIMP)-2 to MMP-9. MK0626 did not affect aortic IL-6 or TNF-α expression in this study.…”

Role of Adipokines and Perivascular Adipose Tissue in Abdominal Aortic Aneurysm: A Systematic Review and Meta-Analysis of Animal and Human Observational Studies

“…Two studies matched cases and controls for age (33,34) and sex (32,34). Three studies reported that controls were healthy (30,32,34). A case-control study reported that plasma DPP-4 enzyme activity was significantly increased in both large and small AAA patients compared to controls and positively correlated with AAA diameter (32) ( Table 3A).…”