glucagon-like-peptide-1 and Aortic-Diseases

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