exenatide and Aortic-Diseases

Dipeptidyl peptidase-4 (DPP-4) inhibitors have various cellular effects that are associated with vascular protection. Here, we examined whether teneligliptin alters the pro-inflammatory phenotype of perivascular adipose tissue (PVAT) and inhibits atherogenesis.. Teneligliptin (60mg/kg/day) was administered orally to apolipoprotein-E-deficient (ApoE. Teneligliptin inhibited atherogenesis with attenuation of the inflammatory phenotype in PVAT. A GLP-1 analog suppressed pro-inflammatory activation of macrophages and adipocytes. Suppression of the pro-inflammatory phenotype of PVAT might contribute, at least partially, to the cardioprotective effects of teneligliptin.

Topics: 3T3-L1 Cells; Adipose Tissue; Animals; Anti-Inflammatory Agents; Aorta; Aortic Diseases; Apolipoproteins E; Atherosclerosis; Cytokines; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Disease Models, Animal; Exenatide; Female; Genetic Predisposition to Disease; Incretins; Inflammation Mediators; Macrophage Activation; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Oxidative Stress; Peptides; Phenotype; Plaque, Atherosclerotic; Pyrazoles; RAW 264.7 Cells; Signal Transduction; Thiazolidines; Time Factors; Vasodilation; Venoms

Exposure to psychosocial stress is a risk factor for cardiovascular disorders. Because the glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonist prevents cardiovascular injury, we investigated the beneficial effects and mechanism of the GLP-1 analogue exenatide on stress-related vascular senescence and atherosclerosis in apolipoprotein E-deficient (ApoE. ApoE. Chronic stress enhanced vascular endothelial senescence and atherosclerotic plaque growth. The stress increased the levels of plasma depeptidyl peptidase-4 activity and decreased the levels of plasma GLP-1 and both plasma and adipose adiponectin (APN). As compared with the mice subjected to stress alone, the exenatide-treated mice had decreased plaque microvessel density, macrophage accumulation, broken elastin, and enhanced plaque collagen volume, and lowered levels of peroxisome proliferator-activated receptor-α, gp91phox osteopontin, C-X-C chemokine receptor-4, toll-like receptor-2 (TLR2), TLR4, and cathepsins K, L, and S mRNAs and/or proteins. Exenatide reduced aortic matrix metalloproteinase-9 (MMP-9) and MMP-2 gene expression and activities. Exenatide also stimulated APN expression of preadipocytes and inhibited ox-low density lipoprotein-induced foam cell formation of monocytes in stressed mice.. These results indicate that the exenatide-mediated beneficial vascular actions are likely attributable, at least in part, to the enhancement of APN production and the attenuation of plaque oxidative stress, inflammation, and proteolysis in ApoE

Topics: Adiponectin; Age Factors; Animals; Aorta; Aortic Diseases; Atherosclerosis; Cells, Cultured; Cellular Senescence; Chronic Disease; Diet, High-Fat; Dipeptidyl Peptidase 4; Disease Models, Animal; Endothelial Cells; Exenatide; Foam Cells; Genetic Predisposition to Disease; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Incretins; Inflammation Mediators; Male; Mice, Knockout, ApoE; Oxidative Stress; Peptide Hydrolases; Peptides; Phenotype; Plaque, Atherosclerotic; Proteolysis; Signal Transduction; Stress, Psychological; Venoms