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
ObjectivesExposure 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 v...
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.687868/full |
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| author | Yanna Lei Qingsong Cui Guang Yang Limei Piao Aiko Inoue Hongxian Wu Xiang Li Masafumi Kuzuya Masafumi Kuzuya Xian Wu Cheng Xian Wu Cheng |
| author_facet | Yanna Lei Qingsong Cui Guang Yang Limei Piao Aiko Inoue Hongxian Wu Xiang Li Masafumi Kuzuya Masafumi Kuzuya Xian Wu Cheng Xian Wu Cheng |
| author_sort | Yanna Lei |
| collection | DOAJ |
| description | ObjectivesExposure 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 Results6-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, p47phox, p47phox, gp91phox, 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.ConclusionThese 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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| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-14T22:28:21Z |
| publishDate | 2021-07-01 |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-ad5a938714e44c9eabdc39d6d0be2cb62022-12-21T22:45:17ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-07-01910.3389/fcell.2021.687868687868Statins Mitigate Stress-Related Vascular Aging and Atherosclerosis in apoE-Deficient Mice Fed High Fat-Diet: The Role of Glucagon-Like Peptide-1/Adiponectin AxisYanna Lei0Qingsong Cui1Guang Yang2Limei Piao3Aiko Inoue4Hongxian Wu5Xiang Li6Masafumi Kuzuya7Masafumi Kuzuya8Xian Wu Cheng9Xian Wu Cheng10Department of Intensive Care Unit, Yanbian University Hospital, Yanjin, ChinaDepartment of Intensive Care Unit, Yanbian University Hospital, Yanjin, ChinaDepartment of Cardiology and Hypertension, Yanbian University Hospital, Yanjin, ChinaDepartment of Cardiology and Hypertension, Yanbian University Hospital, Yanjin, ChinaInstitute of Innovation for Future Society, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Cardiology, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Intensive Care Unit, Yanbian University Hospital, Yanjin, ChinaInstitute of Innovation for Future Society, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Community Healthcare & Geriatrics, Nagoya University Graduate School of Medicine, Nagoya, JapanDepartment of Intensive Care Unit, Yanbian University Hospital, Yanjin, ChinaInstitute of Innovation for Future Society, Nagoya University Graduate School of Medicine, Nagoya, JapanObjectivesExposure 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 Results6-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, p47phox, p47phox, gp91phox, 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.ConclusionThese 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.https://www.frontiersin.org/articles/10.3389/fcell.2021.687868/fullchronic stressstatinsatherosclerosisinflammationadiponectin |
| spellingShingle | Yanna Lei Qingsong Cui Guang Yang Limei Piao Aiko Inoue Hongxian Wu Xiang Li Masafumi Kuzuya Masafumi Kuzuya Xian Wu Cheng Xian Wu Cheng 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 Frontiers in Cell and Developmental Biology chronic stress statins atherosclerosis inflammation adiponectin |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | chronic stress statins atherosclerosis inflammation adiponectin |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.687868/full |
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