Dipeptidyl Peptidase-IV Inhibition for the Treatment of Cardiovascular Disease　- Recent Insights Focusing on Angiogenesis and Neovascularization.
Dipeptidyl peptidase IV (DPP-IV) is a complex enzyme that acts as a membrane-anchored cell surface exopeptidase and transmits intracellular signals through a small intracellular tail. DPP-IV exists in human blood in a soluble form, and truncates a large number of peptide hormones, chemokines, cytokines, and growth factors in vitro and in vivo. DPP-IV has gained considerable interest as a therapeutic target, and a variety of DPP-IV inhibitors that prolong the insulinotropic effects of glucagon-like peptide-1 (GLP-1) are widely used in clinical settings as antidiabetic drugs. Indeed, DPP-IV is upregulated in proinflammatory states, including obesity and cardiovascular disease with and without diabetes mellitus. Consistent with this maladaptive role, DPP-IV inhibitors seem to exert a protective role in cardiovascular disease. In addition to their GLP-1-dependent vascular protective actions, DPP-IV inhibitors exhibit GLP-1-independent beneficial effects on angiogenesis/neovascularization via several signaling pathways (e.g., stromal cell-derived factor-1α/C-X-C chemokine receptor type-4, vascular endothelial growth factor-A/endothelial nitric oxide synthase, etc.). This review focuses on recent findings in this field, highlighting the role of DPP-IV in therapeutic angiogenesis/neovascularization in ischemic heart disease and peripheral artery disease.
Department of ICU, Yanbian University Hospital.
Yanna
Y
Lei
Department of Public Health, Guilin Medical College.
Lina
L
Hu
Department of Cardiology, Yanbian University Hospital.
Guang
G
Yang
Department of Cardiology, Yanbian University Hospital.
Limei
L
Piao
Department of ICU, Yanbian University Hospital.
Minggen
M
Jin
Department of Cardiology, Yanbian University Hospital.|Institute of Innovation for Future Society, Nagoya University.|Department of Cardiovascular Internal Medicine, Kyung Hee University Hospital, Kyung Hee University.
Xianwu
X
Cheng
D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006801:Humans; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D058729:Peripheral Arterial Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*
D054873:Dipeptidyl-Peptidase IV Inhibitors; D052216:Glucagon-Like Peptide 1
Angiogenesis; Dipeptidyl peptidase-IV; Endothelial cells; Endothelial progenitor cells; Stromal cell-derived factor-1