Statins Mitigate Stress-Related Vascular Aging and Atherosclerosis in apoE-Deficient Mice Fed High Fat-Diet: The Role of Glucagon-Like Peptide-1/Adiponectin Axis

• DOI: 10.3389/fcell.2021.687868
• Publication Date: 2021-07-21T14:57:04Z
• Authors: Yanna Lei; Qingsong Cui; Guang Yang; Limei Piao; Aiko Inoue; Hongxian Wu; Xiang Li; Masafumi Kuzuya; Xian Wu Cheng
• Keywords: Pitavastatin; Apolipoprotein E

Exposure to chronic psychosocial stress is a risk factor for atherosclerotic cardiovascular diseases. Given that the 3-hydroxy-3-methylglutaryl-coenzyme reductase inhibitor statins prevent atherogenesis, we evaluated whether pitavastatin prevents stress- and high fat diet-induced vascular senescence atherogenesis in apolipoprotein E-deficient (ApoE-/-) mice, with special focus on glucagon-like peptide-1 (GLP-1)/adiponectin (APN) axis.6-week-old ApoE-/- mice loaded high-fat diet were randomly assigned into non-stress (n = 12) 13) groups 12 weeks. Non-stress control left undisturbed. Chronic accelerated diet-induce arterial plaque growth. The lowered levels of circulating GLP-1 as well adipose plasma APN. As compared alone pitavastatin-treated had reduced macrophage infiltration, elastin fragments, increased collagen volume, osteopontin, toll-like receptor-2/-4, chemoattractant protein-1, C-X-C chemokine receptor-4, p47 phox , gp91 cathepsins S, p16, p21, mRNAs and/or proteins. Pitavastatin APN suppressed matrix metalloproteinase-2/-9 gene expressions activities aortas. Finally, protective effect was abrogated by blocking.These findings suggested pitavastatin-mediated pleiotropic vasculoprotective effects are likely attributable, at least part, elevation inhibition inflammation, oxidative stress, proteolysis received conditions.