期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.687868
关键词
chronic stress; statins; atherosclerosis; inflammation; adiponectin
资金
- National Natural Science Foundation of China [81770485, 81560240, 81800380, 82060052]
- Young Investigation Foundation of Yanbian University [2019-39]
- Fudan University Hospital [2018ZSQN03]
- 135 science and technology project of Jilin Provincial Department of Education [JJKH20200528KJ]
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [20H03574]
- Grants-in-Aid for Scientific Research [20H03574] Funding Source: KAKEN
The study demonstrates that pitavastatin can prevent vascular senescence and atherogenesis induced by chronic stress and high fat diet in mice, potentially by increasing GLP-1 and APN levels and suppressing plaque inflammation and oxidative stress.
Objectives: 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 chronic stress- and high fat diet-induced vascular senescence and atherogenesis in apolipoprotein E-deficient (ApoE(-/-)) mice, with a special focus on glucagon-like peptide-1 (GLP-1)/adiponectin (APN) axis. Methods and Results: 6-week-old ApoE(-/-) mice loaded a high-fat diet were randomly assigned into non-stress (n = 12) and stress (n = 13) groups for 12 weeks. Non-stress control mice were left undisturbed. Chronic stress accelerated high fat diet-induce arterial senescence and atherosclerotic plaque growth. The chronic stress lowered the levels of circulating GLP-1 as well as adipose and plasma APN. As compared with the stress alone mice, the pitavastatin-treated mice had reduced macrophage infiltration, elastin fragments, and increased plaque collagen volume, and lowered levels of osteopontin, toll-like receptor-2/-4, macrophage chemoattractant protein-1, C-X-C chemokine receptor-4, p47(phox), p47(phox), gp91(phox), cathepsins S, p16, and p21, mRNAs and/or proteins. Pitavastatin increased plasma GLP-1 and APN levels and suppressed matrix metalloproteinase-2/-9 gene expressions and activities in the aortas. Finally, the protective effect of pitavastatin was abrogated by APN blocking. Conclusion: These findings suggested that the pitavastatin-mediated pleiotropic vasculoprotective effects are likely attributable, at least in part, to the elevation of GLP-1 and APN levels and the inhibition of diet-induced plaque inflammation, oxidative stress, and proteolysis in ApoE(-/-) mice received chronic stress conditions.
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