Dipeptidyl Peptidase-IV Inhibition for the Treatment of Cardiovascular Disease　― Recent Insights Focusing on Angiogenesis and Neovascularization ―

Chronic Psychological Stress Accelerates Vascular Senescence and Impairs Ischemia‐Induced Neovascularization: The Role of Dipeptidyl Peptidase‐4/Glucagon‐Like Peptide‐1‐Adiponectin Axis

“…Dipeptidyl peptidase 4 (DPP4) is a complex enzyme that acts as a membrane‐anchored cell surface exopeptidase that transmits intracellular signals through a small intracellular tail . DPP4 has gained considerable interest as a therapeutic target, and a variety of DPP4 inhibitors that prolong the insulinotropic effects of glucagon‐like peptide‐1 (GLP‐1) are widely used in clinical settings as a new class of antidiabetic drugs .…”

Prognostic value of plasma DPP4 activity in ST-elevation myocardial infarction

“…Our group previously found that GLP-1 analog use before PCI associated with improved left ventricular ejection fraction rates in MI patients after a 3-month follow-up [37, 38]. Moreover, DPP4 protein has additional substrates that participate in responses to ischemic heart disease, such as stromal cell-derived factor-1 alpha (SDF1α), neuropeptide Y and substance P [39]. The plasma levels of these substrates associated with adverse events after MI [40–42].…”

Dose rectification of an imbalance between DPP4 and GLP‐1 ameliorates chronic stress‐related vascular aging and atherosclerosis?

“…Dipeptidyl peptidase 4 (DPP4) is a complex enzyme that acts as a membrane-anchored cell surface exopeptidase that transmits intracellular signals through a small intracellular tail. 19 DPP4 has gained considerable interest as a therapeutic target, and DPP4 inhibitors that extend the insulinotropic effects of glucagon-like peptide-1 (GLP-1) are widely used as a new class of antidiabetes drugs. 20 In addition to GLP-1-dependent effects on the cardiometabolic risk profile, DPP4 inhibition exhibits vascular protective benefits via the regulation of several substrate factor activities (eg., stromal cell-derived factor-1α, colony-stimulating factor, granulocyte-colony-stimulating factor, neuropeptide Y, granulocyte macrophage-colony-stimulating factor, and high-mobility group box 1).…”

“…20 In addition to GLP-1-dependent effects on the cardiometabolic risk profile, DPP4 inhibition exhibits vascular protective benefits via the regulation of several substrate factor activities (eg., stromal cell-derived factor-1α, colony-stimulating factor, granulocyte-colony-stimulating factor, neuropeptide Y, granulocyte macrophage-colony-stimulating factor, and high-mobility group box 1). 19 A recent study reported that individuals with and without diabetes mellitus had increased plasma DPP4 levels and decreased plasma GLP-1 levels. 21 In mice and rats, chronic stress increased plasma and tissue DPP4 activities and decreased plasma and brain GLP-1 levels, 22 suggesting an imbalance between DPP4 and GLP-1 as a potential therapeutic target in the management of vascular aging and atherosclerosis in animals under experimental stress conditions.…”

“…Although a growing body of evidence suggests that DPP4 plays a critical role in the initiation and progression of CVD, 19 little is known about the functional relevance of this exopeptidase as a transmembrane protease in the pathogenesis of stress-related vascular aging and atherosclerosis. Chronic variable stress has been shown to produce harmful changes in plasma and tissue DPP4 levels.…”