AUTHOR=Wang Mengyu , Xing Junhui , Liu Mengduan , Gao Mingming , Liu Yangyang , Li Xiaowei , Hu Liang , Zhao Xiaoyan , Liao Jiawei , Liu George , Dong Jianzeng 

TITLE=Deletion of Seipin Attenuates Vascular Function and the Anticontractile Effect of Perivascular Adipose Tissue

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.706924

DOI=10.3389/fcvm.2021.706924

ISSN=2297-055X

ABSTRACT=<p><italic>Seipin</italic> locates in endoplasmic reticulum (ER) and regulates adipogenesis and lipid droplet formation. Deletion of <italic>Seipin</italic> 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 <italic>Seipin</italic> in mediating the anticontractile effect of PVAT and vascular function. <italic>Seipin</italic> expression in PVAT and associated vessels were detected by qPCR and western-blot. <italic>Seipin</italic> is highly expressed in PVAT, but hardly in vessels. Structural and functional alterations of PVAT and associated vessels were compared between <italic>Seipin</italic><sup>−/−</sup> mice and WT mice. In <italic>Seipin</italic><sup>−/−</sup> 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 <italic>Seipin</italic><sup>−/−</sup> mice were mounted on a wire myograph. Vasoconstriction and vasodilation were studied in vessels with and without PVAT. WT PVAT augmented relaxation but not <italic>Seipin</italic><sup>−/−</sup> PVAT, which suggest impaired anticontractile function in PVAT of <italic>Seipin</italic><sup>−/−</sup> mice. Thoracic aorta and mesenteric artery from <italic>Seipin</italic><sup>−/−</sup> mice had impaired contractility in response to phenylephrine (PHE) and relaxation to acetylcholine (Ach). In conclusion, <italic>Seipin</italic> deficiency caused abnormalities in PVAT morphology and vascular functions. Our data demonstrated for the first time that <italic>Seipin</italic> plays a critical role in maintaining PVAT function and vascular homeostasis.</p>