title: Cardiovascular effects of DPP-4 inhibition: beyond GLP-1.
abstract: Dipeptydil-peptidase-4 (DPP-4) inhibitors are available as oral anti-hyperglycemic drugs for the treatment of type 2 diabetes. Their metabolic effect is mediated through sparing incretin hormones (such as glucagon-like peptide-1, GLP-1) from the rapid degradation by DPP-4. In turn, GLP-1 improves meal-stimulated insulin secretion by pancreatic β-cells thus reducing hyperglycemia. It has been shown that GLP-1 signaling is also active in the cardiovascular system, where it may exert beneficial effects. However, DPP-4 has several non-incretin substrates, and its immunomodulatory activity is known from decades. DPP-4 physiologically cleaves cytokines, chemokines and neuropeptides involved in inflammation, immunity, and vascular function. Owing to these off-target mechanisms, DPP-4 inhibitors hold promise for cardiovascular protection, but may also face unexpected side effects. Herein, we review available data on the cardiovascular effects of DPP-4 inhibitors, with a special interest in GLP-1-independent mechanisms. The modulation of endothelial progenitor cells, inflammatory pathway and ischemic response emerges as the major cardiovascular target of DPP-4 inhibitors.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Padova, Faculty of Medicine, Padova, Italy. gianpaolo.fadini@unipd.it
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Fadini
authors.forename: Angelo
authors.initials: A
authors.lastname: Avogaro
mesh_terms: D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects* / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D052216:Glucagon-Like Peptide 1; D018819:Dipeptidyl Peptidase 4