An emerging role of dipeptidyl peptidase 4 (DPP4) beyond glucose control: Potential implications in cardiovascular disease

Jixin Zhong, Xiaoquan Rao, Sanjay Rajagopalan

Research output: Contribution to journalReview article

125 Citations (Scopus)

Abstract

The introduction of dipeptidyl peptidase 4 (DPP4) inhibitors for the treatment of Type 2 diabetes acknowledges the fundamental importance of incretin hormones in the regulation of glycemia. Small molecule inhibitors of DPP4 exert their effects via inhibition of enzymatic degradation of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). The widespread expression of DPP4 in tissues such as the vasculature and immune cells suggests that this protein may play a role in cardiovascular function. DPP4 is known to exert its effects via both enzymatic and non-enzymatic mechanisms. A soluble form of DPP4 lacking the cytoplasmic and transmembrane domain has also been recently recognized. Besides enzymatic inactivation of incretins, DPP4 also mediates degradation of many chemokines and neuropeptides. The non-enzymatic function of DPP4 plays a critical role in providing co-stimulatory signals to T cells via adenosine deaminase (ADA). DPP4 may also regulate inflammatory responses in innate immune cells such as monocytes and dendritic cells. The multiplicity of functions and targets suggests that DPP4 may play a distinct role aside from its effects on the incretin axis. Indeed recent studies in experimental models of atherosclerosis provide evidence for a robust effect for these drugs in attenuating inflammation and plaque development. Several prospective randomized controlled clinical trials in humans with established atherosclerosis are testing the effects of DPP4 inhibition on hard cardiovascular events.

Original languageEnglish (US)
Pages (from-to)305-314
Number of pages10
JournalAtherosclerosis
Volume226
Issue number2
DOIs
StatePublished - Feb 1 2013
Externally publishedYes

Fingerprint

Dipeptidyl Peptidase 4
Cardiovascular Diseases
Glucose
Incretins
Dipeptidyl-Peptidase IV Inhibitors
Atherosclerosis
Gastric Inhibitory Polypeptide
Adenosine Deaminase
Glucagon-Like Peptide 1
Neuropeptides
Chemokines
Innate Immunity
Dendritic Cells
Type 2 Diabetes Mellitus
Monocytes
Theoretical Models
Randomized Controlled Trials
Hormones
Inflammation
T-Lymphocytes

Keywords

  • Atherosclerosis
  • CD26
  • DPP4
  • Inflammation
  • Type 2 diabetes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

An emerging role of dipeptidyl peptidase 4 (DPP4) beyond glucose control : Potential implications in cardiovascular disease. / Zhong, Jixin; Rao, Xiaoquan; Rajagopalan, Sanjay.

In: Atherosclerosis, Vol. 226, No. 2, 01.02.2013, p. 305-314.

Research output: Contribution to journalReview article

@article{cb78bcb0687a45d0b76ccb0ad1349fb2,
title = "An emerging role of dipeptidyl peptidase 4 (DPP4) beyond glucose control: Potential implications in cardiovascular disease",
abstract = "The introduction of dipeptidyl peptidase 4 (DPP4) inhibitors for the treatment of Type 2 diabetes acknowledges the fundamental importance of incretin hormones in the regulation of glycemia. Small molecule inhibitors of DPP4 exert their effects via inhibition of enzymatic degradation of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). The widespread expression of DPP4 in tissues such as the vasculature and immune cells suggests that this protein may play a role in cardiovascular function. DPP4 is known to exert its effects via both enzymatic and non-enzymatic mechanisms. A soluble form of DPP4 lacking the cytoplasmic and transmembrane domain has also been recently recognized. Besides enzymatic inactivation of incretins, DPP4 also mediates degradation of many chemokines and neuropeptides. The non-enzymatic function of DPP4 plays a critical role in providing co-stimulatory signals to T cells via adenosine deaminase (ADA). DPP4 may also regulate inflammatory responses in innate immune cells such as monocytes and dendritic cells. The multiplicity of functions and targets suggests that DPP4 may play a distinct role aside from its effects on the incretin axis. Indeed recent studies in experimental models of atherosclerosis provide evidence for a robust effect for these drugs in attenuating inflammation and plaque development. Several prospective randomized controlled clinical trials in humans with established atherosclerosis are testing the effects of DPP4 inhibition on hard cardiovascular events.",
keywords = "Atherosclerosis, CD26, DPP4, Inflammation, Type 2 diabetes",
author = "Jixin Zhong and Xiaoquan Rao and Sanjay Rajagopalan",
year = "2013",
month = "2",
day = "1",
doi = "10.1016/j.atherosclerosis.2012.09.012",
language = "English (US)",
volume = "226",
pages = "305--314",
journal = "Atherosclerosis",
issn = "0021-9150",
publisher = "Elsevier Ireland Ltd",
number = "2",

}

TY - JOUR

T1 - An emerging role of dipeptidyl peptidase 4 (DPP4) beyond glucose control

T2 - Potential implications in cardiovascular disease

AU - Zhong, Jixin

AU - Rao, Xiaoquan

AU - Rajagopalan, Sanjay

PY - 2013/2/1

Y1 - 2013/2/1

N2 - The introduction of dipeptidyl peptidase 4 (DPP4) inhibitors for the treatment of Type 2 diabetes acknowledges the fundamental importance of incretin hormones in the regulation of glycemia. Small molecule inhibitors of DPP4 exert their effects via inhibition of enzymatic degradation of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). The widespread expression of DPP4 in tissues such as the vasculature and immune cells suggests that this protein may play a role in cardiovascular function. DPP4 is known to exert its effects via both enzymatic and non-enzymatic mechanisms. A soluble form of DPP4 lacking the cytoplasmic and transmembrane domain has also been recently recognized. Besides enzymatic inactivation of incretins, DPP4 also mediates degradation of many chemokines and neuropeptides. The non-enzymatic function of DPP4 plays a critical role in providing co-stimulatory signals to T cells via adenosine deaminase (ADA). DPP4 may also regulate inflammatory responses in innate immune cells such as monocytes and dendritic cells. The multiplicity of functions and targets suggests that DPP4 may play a distinct role aside from its effects on the incretin axis. Indeed recent studies in experimental models of atherosclerosis provide evidence for a robust effect for these drugs in attenuating inflammation and plaque development. Several prospective randomized controlled clinical trials in humans with established atherosclerosis are testing the effects of DPP4 inhibition on hard cardiovascular events.

AB - The introduction of dipeptidyl peptidase 4 (DPP4) inhibitors for the treatment of Type 2 diabetes acknowledges the fundamental importance of incretin hormones in the regulation of glycemia. Small molecule inhibitors of DPP4 exert their effects via inhibition of enzymatic degradation of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). The widespread expression of DPP4 in tissues such as the vasculature and immune cells suggests that this protein may play a role in cardiovascular function. DPP4 is known to exert its effects via both enzymatic and non-enzymatic mechanisms. A soluble form of DPP4 lacking the cytoplasmic and transmembrane domain has also been recently recognized. Besides enzymatic inactivation of incretins, DPP4 also mediates degradation of many chemokines and neuropeptides. The non-enzymatic function of DPP4 plays a critical role in providing co-stimulatory signals to T cells via adenosine deaminase (ADA). DPP4 may also regulate inflammatory responses in innate immune cells such as monocytes and dendritic cells. The multiplicity of functions and targets suggests that DPP4 may play a distinct role aside from its effects on the incretin axis. Indeed recent studies in experimental models of atherosclerosis provide evidence for a robust effect for these drugs in attenuating inflammation and plaque development. Several prospective randomized controlled clinical trials in humans with established atherosclerosis are testing the effects of DPP4 inhibition on hard cardiovascular events.

KW - Atherosclerosis

KW - CD26

KW - DPP4

KW - Inflammation

KW - Type 2 diabetes

UR - http://www.scopus.com/inward/record.url?scp=84872424922&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84872424922&partnerID=8YFLogxK

U2 - 10.1016/j.atherosclerosis.2012.09.012

DO - 10.1016/j.atherosclerosis.2012.09.012

M3 - Review article

C2 - 23083681

AN - SCOPUS:84872424922

VL - 226

SP - 305

EP - 314

JO - Atherosclerosis

JF - Atherosclerosis

SN - 0021-9150

IS - 2

ER -