Aug 19, 2015

Dipeptidyl peptidase-4 inhibitor, linagliptin, ameliorates endothelial dysfunction and atherogenesis in normoglycemic apolipoprotein-E deficient mice

Vascular Pharmacology
Hotimah Masdan SalimMasataka Sata


Dipeptidyl peptidase-4 (DPP-4) inhibitors have vasoprotective effects. This study investigated whether a recently approved DPP-4 inhibitor, linagliptin (Lina), suppresses atherogenesis in non-diabetic apolipoprotein-E deficient (ApoE(-/-)) mice, and examined its effects on endothelial function. Lina (10mg/kg/day) was administered orally to ApoE(-/-) mice for 20weeks. Lina reduced atherogenesis without alteration of metabolic parameters including blood glucose level compared with control (P<0.05). Results of immunohistochemical analyses and quantitative RT-PCR demonstrated that Lina significantly decreased inflammatory molecule expression and macrophage infiltration in the atherosclerotic aorta. Lina administration to ApoE(-/-) mice for 9weeks ameliorated endothelium-dependent vasodilation compared with that in untreated mice. Plasma active glucagon-like peptide-1 (GLP-1) level was significantly higher in the treated group (P<0.05). Exendin-4 (Ex-4), a GLP-1 analog, ameliorated endothelium-dependent vasodilation impaired by palmitic acid (PA) in wild-type mouse aortic segments. Ex-4 promoted phosphorylation of eNOS(Ser1177) and Akt, both of which were abrogated by PA, in human umbilical vein endothelial cells. In addition, Lina ...Continue Reading

Mentioned in this Paper

Metabolic Process, Cellular
Real-Time Polymerase Chain Reaction
Diabetes Mellitus, Non-Insulin-Dependent
Vascular Inflammations
Tissue Membrane

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