Deletion of Seipin Attenuates Vascular Function and the Anticontractile Effect of Perivascular Adipose Tissue
Seipin locates in endoplasmic reticulum (ER) and regulates adipogenesis and lipid droplet formation. Deletion of Seipin has been well-demonstrated to cause severe general lipodystrophy, however, its role in maintaining perivascular adipose tissue (PVAT) and vascular homeostasis has not been directly...
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Frontiers Media S.A.
2021-08-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2021.706924/full |
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author | Mengyu Wang Junhui Xing Mengduan Liu Mingming Gao Yangyang Liu Xiaowei Li Liang Hu Xiaoyan Zhao Jiawei Liao George Liu Jianzeng Dong Jianzeng Dong |
author_facet | Mengyu Wang Junhui Xing Mengduan Liu Mingming Gao Yangyang Liu Xiaowei Li Liang Hu Xiaoyan Zhao Jiawei Liao George Liu Jianzeng Dong Jianzeng Dong |
author_sort | Mengyu Wang |
collection | DOAJ |
description | Seipin locates in endoplasmic reticulum (ER) and regulates adipogenesis and lipid droplet formation. Deletion of Seipin has been well-demonstrated to cause severe general lipodystrophy, however, its role in maintaining perivascular adipose tissue (PVAT) and vascular homeostasis has not been directly assessed. In the present study, we investigated the role of Seipin in mediating the anticontractile effect of PVAT and vascular function. Seipin expression in PVAT and associated vessels were detected by qPCR and western-blot. Seipin is highly expressed in PVAT, but hardly in vessels. Structural and functional alterations of PVAT and associated vessels were compared between Seipin−/− mice and WT mice. In Seipin−/− mice, aortic and mesenteric PVAT were significantly reduced in mass and adipose-derived relaxing factors (ADRFs) secretion, but increased in macrophage infiltration and ER stress, as compared with those in WT mice. Aortic and mesenteric artery rings from WT and Seipin−/− mice were mounted on a wire myograph. Vasoconstriction and vasodilation were studied in vessels with and without PVAT. WT PVAT augmented relaxation but not Seipin−/− PVAT, which suggest impaired anticontractile function in PVAT of Seipin−/− mice. Thoracic aorta and mesenteric artery from Seipin−/− mice had impaired contractility in response to phenylephrine (PHE) and relaxation to acetylcholine (Ach). In conclusion, Seipin deficiency caused abnormalities in PVAT morphology and vascular functions. Our data demonstrated for the first time that Seipin plays a critical role in maintaining PVAT function and vascular homeostasis. |
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spelling | doaj.art-860d3ca5f2b54a93a3b8fce06be1c1c92022-12-21T20:02:56ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2021-08-01810.3389/fcvm.2021.706924706924Deletion of Seipin Attenuates Vascular Function and the Anticontractile Effect of Perivascular Adipose TissueMengyu Wang0Junhui Xing1Mengduan Liu2Mingming Gao3Yangyang Liu4Xiaowei Li5Liang Hu6Xiaoyan Zhao7Jiawei Liao8George Liu9Jianzeng Dong10Jianzeng Dong11Department of Cardiology, Henan Key Laboratory of Hereditary Cardiovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Cardiology, Henan Key Laboratory of Hereditary Cardiovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Cardiology, Henan Key Laboratory of Hereditary Cardiovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaLaboratory of Lipid Metabolism, Hebei Medical University, Shijiazhuang, ChinaDepartment of Cardiology, Henan Key Laboratory of Hereditary Cardiovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Cardiology, Henan Key Laboratory of Hereditary Cardiovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Cardiology, Henan Key Laboratory of Hereditary Cardiovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Cardiology, Henan Key Laboratory of Hereditary Cardiovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, ChinaKey Laboratory of Molecular Cardiovascular Sciences, Peking University Health Science Center, School of Basic Medical Sciences, Institute of Cardiovascular Sciences, Ministry of Education, Beijing, ChinaDepartment of Cardiology, Henan Key Laboratory of Hereditary Cardiovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Cardiology, National Clinical Research Centre for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, ChinaSeipin locates in endoplasmic reticulum (ER) and regulates adipogenesis and lipid droplet formation. Deletion of Seipin has been well-demonstrated to cause severe general lipodystrophy, however, its role in maintaining perivascular adipose tissue (PVAT) and vascular homeostasis has not been directly assessed. In the present study, we investigated the role of Seipin in mediating the anticontractile effect of PVAT and vascular function. Seipin expression in PVAT and associated vessels were detected by qPCR and western-blot. Seipin is highly expressed in PVAT, but hardly in vessels. Structural and functional alterations of PVAT and associated vessels were compared between Seipin−/− mice and WT mice. In Seipin−/− mice, aortic and mesenteric PVAT were significantly reduced in mass and adipose-derived relaxing factors (ADRFs) secretion, but increased in macrophage infiltration and ER stress, as compared with those in WT mice. Aortic and mesenteric artery rings from WT and Seipin−/− mice were mounted on a wire myograph. Vasoconstriction and vasodilation were studied in vessels with and without PVAT. WT PVAT augmented relaxation but not Seipin−/− PVAT, which suggest impaired anticontractile function in PVAT of Seipin−/− mice. Thoracic aorta and mesenteric artery from Seipin−/− mice had impaired contractility in response to phenylephrine (PHE) and relaxation to acetylcholine (Ach). In conclusion, Seipin deficiency caused abnormalities in PVAT morphology and vascular functions. Our data demonstrated for the first time that Seipin plays a critical role in maintaining PVAT function and vascular homeostasis.https://www.frontiersin.org/articles/10.3389/fcvm.2021.706924/fullSeipinlipodystrophyPVATvascular functionanticontractile function |
spellingShingle | Mengyu Wang Junhui Xing Mengduan Liu Mingming Gao Yangyang Liu Xiaowei Li Liang Hu Xiaoyan Zhao Jiawei Liao George Liu Jianzeng Dong Jianzeng Dong Deletion of Seipin Attenuates Vascular Function and the Anticontractile Effect of Perivascular Adipose Tissue Frontiers in Cardiovascular Medicine Seipin lipodystrophy PVAT vascular function anticontractile function |
title | Deletion of Seipin Attenuates Vascular Function and the Anticontractile Effect of Perivascular Adipose Tissue |
title_full | Deletion of Seipin Attenuates Vascular Function and the Anticontractile Effect of Perivascular Adipose Tissue |
title_fullStr | Deletion of Seipin Attenuates Vascular Function and the Anticontractile Effect of Perivascular Adipose Tissue |
title_full_unstemmed | Deletion of Seipin Attenuates Vascular Function and the Anticontractile Effect of Perivascular Adipose Tissue |
title_short | Deletion of Seipin Attenuates Vascular Function and the Anticontractile Effect of Perivascular Adipose Tissue |
title_sort | deletion of seipin attenuates vascular function and the anticontractile effect of perivascular adipose tissue |
topic | Seipin lipodystrophy PVAT vascular function anticontractile function |
url | https://www.frontiersin.org/articles/10.3389/fcvm.2021.706924/full |
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