Deletion of Seipin Attenuates Vascular Function and the Anticontractile Effect of Perivascular Adipose Tissue.
Deletion of Seipin Attenuates Vascular Function and the Anticontractile Effect of Perivascular Adipose Tissue.
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Seipin 缺失会减弱血管功能和血管周围脂肪组织的抗收缩作用
DOI：
10.3389/fcvm.2021.706924
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发表时间：
2021
影响因子：
3.6
通讯作者：
Dong J
中科院分区：
文献类型：
--
作者：
Wang M;Xing J;Liu M;Gao M;Liu Y;Li X;Hu L;Zhao X;Liao J;Liu G;Dong J
Seipin定位于内质网，调节脂肪形成和脂滴形成。Seipin的缺失已被充分证明会导致严重的全身脂肪代谢障碍，然而，其在维持血管周围脂肪组织（PVAT）和血管稳态中的作用尚未直接评估。在本研究中，我们研究了Seipin在介导PVAT的抗收缩作用和血管功能中的作用。通过qPCR和western-blot检测PVAT和相关血管中的Seipin表达。Seipin在PVAT中高度表达，但在血管中几乎不表达。在Seipin−/−小鼠和WT小鼠之间比较PVAT和相关血管的结构和功能改变。在Seipin−/−小鼠中，与WT小鼠相比，主动脉和肠系膜PVAT的质量和脂肪源性舒张因子（ADRF）分泌显著减少，但巨噬细胞浸润和ER应激增加。将WT和Seipin−/−小鼠的主动脉和肠系膜动脉环固定在钢丝肌描记器上。在有和没有PVAT的血管中研究了血管收缩和血管舒张。WT PVAT增强了舒张，但Seipin−/− PVAT没有，这表明Seipin−/−小鼠的PVAT抗收缩功能受损。Seipin−/−小鼠的胸主动脉和肠系膜动脉对苯肾上腺素（PHE）的收缩性受损，对乙酰胆碱（Ach）的舒张性受损。总之，Seipin缺乏导致PVAT形态和血管功能异常。我们的数据首次表明，Seipin在维持PVAT功能和血管稳态中起着关键作用。
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.