title: Gliptins and their target dipeptidyl peptidase 4: implications for the treatment of vascular disease.
abstract: Gliptins are accepted as a standard therapy for diabetes mellitus today. By inhibition of the enzyme dipeptidyl peptidase 4 (DPP4), gliptins prolong the GLP1-dependent insulin secretion in the pancreatic β-cells and thus support physiological blood glucose control. Various studies have now raised hope for an additional protective effect of pharmacological DPP4 inhibition in vascular diseases. Besides GLP1, especially, the inhibition of SDF1 cleavage has been shown to depict a relevant mechanism to enhance endothelial regeneration and reduce atherosclerosis progression via the SDF1-CXCR4 axis. Furthermore, several clinical trials have now shown an excellent safety profile of gliptin therapy in cardiovascular risk patients. In this review, we give a comprehensive overview on DPP4-dependent vascular functions and pathophysiological mechanisms with a detailed discussion of the underlying molecular mechanisms. We further analyse the role of pharmacological DPP4 inhibitors and their potential therapeutic impact on endothelial function and regeneration besides their effect during atherosclerosis development. Finally, we discuss presently available data from in vitro and in vivo studies with respect to the results of the recent clinical trials in diabetic and non-diabetic patients.
authors.affiliation: Department of Internal Medicine III, Medical University of Innsbruck, Anichstr. 35, 6020 Innsbruck, Austria.
authors.forename: Friederike
authors.initials: F
authors.lastname: Remm
authors.affiliation: Department of Internal Medicine III, Medical University of Innsbruck, Anichstr. 35, 6020 Innsbruck, Austria.
authors.forename: Wolfgang-Michael
authors.initials: WM
authors.lastname: Franz
authors.affiliation: Department of Internal Medicine III, Medical University of Innsbruck, Anichstr. 35, 6020 Innsbruck, Austria mail@med.cbrenner.net.
authors.forename: Christoph
authors.initials: C
authors.lastname: Brenner
mesh_terms: D000818:Animals; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D014652:Vascular Diseases / Q000188:drug therapy* / Q000201:enzymology
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D018819:Dipeptidyl Peptidase 4
keywords: Atherosclerosis; DPP4; Endothelial injury; Gliptins; Vascular disease