The Dipeptidyl Peptidase Family, Prolyl Oligopeptidase, and Prolyl Carboxypeptidase in the Immune System and Inflammatory Disease, Including Atherosclerosis

Abstract

Research from over the past 20 years has implicated dipeptidyl peptidase (DPP) IV and its family members in many processes and different pathologies of the immune system. Most research has been focused on either DPPIV or just a few of its family members. It is, however, essential to consider the entire DPP family when discussing any one of its members. There is a substantial overlap between family members in their substrate specificity, inhibitors, and functions. In this review, we provide a comprehensive discussion on the role of prolyl-specific peptidases DPPIV, FAP, DPP8, DPP9, dipeptidyl peptidase II, prolyl carboxypeptidase, and prolyl oligopeptidase in the immune system and its diseases. We highlight possible therapeutic targets for the prevention and treatment of atherosclerosis, a condition that lies at the frontier between inflammation and cardiovascular disease.

Wound Healing Process, Diabetes and Implications of Dipeptidyl Peptidase IV (DPP IV/CD26)

“…Important physiological functions of DPP IV/CD26 come with interactions with other proteins, such as ADA, substance P, VEGF, IP-10, glucagon and NPY [38]. DPP IV/CD26 plays an important role in wound healing at several levels: via its involvement in degradation of extracellular matrix (ECM), in cell adhesion and migration, and angiogenesis.…”

Untitled

“…Selektivno cijepa N-terminale dipeptide iz proteinskih lanaca s prolinom ili alaninom na pretposljednjem mjestu u aminokiselinskoj sekvenci 27 . Prvi put je identificirana 1966. godine, kada su V. K. Hopsu-Havu i G. G. Glenner otkrili novi enzim histokemijskim ispitivanjima u bubregu štakora, a zatim poslije i u jetri štakora, u bubregu psa i u mnogim drugim tkivima.…”

On Endogenous Angiotensin II Antagonism in Hypertension

“…In this issue of Hypertension, the role of dipeptidyl peptidase III (DPP III) as a new antihypertensive candidate has been characterized in the mice. 1 Similar to DPP III, the carboxy peptidase ACE2 mediates degradation from Ang II to Ang (1-7) and also from Ang I to Ang (1)(2)(3)(4)(5)(6)(7)(8)(9). Both peptides contribute to the antihypertensive/ vasoprotective effects of the counterregulatory RAAS pathway ( Figure).…”

“…8 Within this group, there is a significant connection between their members about substrate specificity, inhibitors, and functions. 8 In Dahl salt-sensitive rats, highsalt diet for 7 days increases blood pressure, and treatment with the DPP IV inhibitor vildagliptin reduces circulating DPP-4 activity, increases plasma glucagon-like peptide 1, and reduces the development of salt-induced hypertension, which is associated to increased urine sodium excretion.…”

“…8 Within this group, there is a significant connection between their members about substrate specificity, inhibitors, and functions. 8 In Dahl salt-sensitive rats, highsalt diet for 7 days increases blood pressure, and treatment with the DPP IV inhibitor vildagliptin reduces circulating DPP-4 activity, increases plasma glucagon-like peptide 1, and reduces the development of salt-induced hypertension, which is associated to increased urine sodium excretion. 9 Together with ACE2 and the abovementioned vasoactive peptides Ang (1-7), Ang (1-9), and alamandine, DPP III is a multifaceted cytosolic oligopeptide N-end cutter that regulates, among others, the Ang II and Ang IV turnover (Figure).…”