Wang Mengyu, Xing Junhui, Liu Mengduan, Gao Mingming, Liu Yangyang, Li Xiaowei, Hu Liang, Zhao Xiaoyan, Liao Jiawei, Liu George, Dong Jianzeng
Department of Cardiology, Henan Key Laboratory of Hereditary Cardiovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Laboratory of Lipid Metabolism, Hebei Medical University, Shijiazhuang, China.
Front Cardiovasc Med. 2021 Aug 2;8:706924. doi: 10.3389/fcvm.2021.706924. eCollection 2021.
locates in endoplasmic reticulum (ER) and regulates adipogenesis and lipid droplet formation. Deletion of 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 in mediating the anticontractile effect of PVAT and vascular function. expression in PVAT and associated vessels were detected by qPCR and western-blot. is highly expressed in PVAT, but hardly in vessels. Structural and functional alterations of PVAT and associated vessels were compared between mice and WT mice. In 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 mice were mounted on a wire myograph. Vasoconstriction and vasodilation were studied in vessels with and without PVAT. WT PVAT augmented relaxation but not PVAT, which suggest impaired anticontractile function in PVAT of mice. Thoracic aorta and mesenteric artery from mice had impaired contractility in response to phenylephrine (PHE) and relaxation to acetylcholine (Ach). In conclusion, deficiency caused abnormalities in PVAT morphology and vascular functions. Our data demonstrated for the first time that plays a critical role in maintaining PVAT function and vascular homeostasis.
定位于内质网(ER)并调节脂肪生成和脂滴形成。已充分证明缺失会导致严重的全身性脂肪营养不良,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得到直接评估。在本研究中,我们研究了在介导PVAT的抗收缩作用和血管功能中的作用。通过qPCR和蛋白质免疫印迹法检测PVAT和相关血管中的表达。在PVAT中高表达,但在血管中几乎不表达。比较了小鼠和野生型(WT)小鼠中PVAT和相关血管的结构和功能改变。与WT小鼠相比,小鼠的主动脉和肠系膜PVAT的质量和脂肪源性舒张因子(ADRFs)分泌显著减少,但巨噬细胞浸润和内质网应激增加。将WT和小鼠的主动脉和肠系膜动脉环安装在血管张力测定仪上。研究了有和没有PVAT的血管中的血管收缩和舒张。WT的PVAT增强舒张,但的PVAT则不然,这表明小鼠PVAT中的抗收缩功能受损。小鼠的胸主动脉和肠系膜动脉对去氧肾上腺素(PHE)的收缩反应和对乙酰胆碱(Ach)的舒张反应受损。总之,缺乏导致PVAT形态和血管功能异常。我们的数据首次证明在维持PVAT功能和血管稳态中起关键作用。