Laboratory of Vascular Biology and Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Arterioscler Thromb Vasc Biol. 2010 Dec;30(12):2568-74. doi: 10.1161/ATVBAHA.110.215525. Epub 2010 Sep 23.
To examine the role of perivascular adipose tissue (PVAT)-derived factors in the regulation of adventitial fibroblast (AF) function in vitro and in vivo.
PVAT is an active component of blood vessels. Bioactive substances released from PVAT play regulatory roles in vascular function. However, their effects on vascular AFs remain unclear. PVAT-conditioned medium stimulated AF migration using a transwell technique, and differentiation was evaluated by α-smooth muscle-actin induction. We identified the secretome of PVAT by liquid chromatography-tandem mass spectrometry. One of the major secretory proteins in PVAT is complement 3 (C3). The C3 antagonist and neutralizing antibody attenuated PVAT-conditioned medium-induced AF migration and differentiation. Similar to PVAT-conditioned medium, C3 recombinant protein stimulated AF migration and differentiation. We demonstrated that the effects of PVAT-derived C3 were mediated by the c-Jun N-terminal kinase pathway. Moreover, we found morphological changes in perivascular adipocytes and increased expression of C3 in PVAT that was tightly associated with adventitial thickening and myofibroblast clustering around PVAT in deoxycorticosterone acetate-salt hypertensive rats.
PVAT-derived C3 stimulated AF migration and differentiation via the c-Jun N-terminal kinase pathway. PVAT-derived C3 may contribute to adventitial remodeling in a deoxycorticosterone acetate-salt hypertensive model.
研究血管外膜脂肪组织（PVAT）衍生因子在体外和体内调节血管外膜成纤维细胞（AF）功能中的作用。
PVAT 是血管的一个活性成分。从 PVAT 释放的生物活性物质在血管功能中发挥调节作用。然而，它们对血管 AF 的影响尚不清楚。PVAT 条件培养基通过 Transwell 技术刺激 AF 迁移，并通过α-平滑肌肌动蛋白诱导来评估分化。我们通过液相色谱-串联质谱鉴定了 PVAT 的分泌组。PVAT 中的主要分泌蛋白之一是补体 3（C3）。C3 拮抗剂和中和抗体减弱了 PVAT 条件培养基诱导的 AF 迁移和分化。类似于 PVAT 条件培养基，C3 重组蛋白刺激 AF 迁移和分化。我们证明了 PVAT 衍生的 C3 的作用是通过 c-Jun N 端激酶途径介导的。此外，我们发现血管外膜脂肪细胞的形态发生变化，并且在血管外膜中 C3 的表达增加，这与去氧皮质酮醋酸盐-盐高血压大鼠中血管外膜周围的血管外膜增厚和肌成纤维细胞聚集密切相关。
PVAT 衍生的 C3 通过 c-Jun N 端激酶途径刺激 AF 迁移和分化。PVAT 衍生的 C3 可能有助于去氧皮质酮醋酸盐-盐高血压模型中的血管外膜重塑。
