Perivascular Adipose Tissue-Derived Complement 3 Is Required for Adventitial Fibroblast Functions and Adventitial Remodeling in Deoxycorticosterone Acetate-Salt Hypertensive Rats
Perivascular Adipose Tissue-Derived Complement 3 Is Required for Adventitial Fibroblast Functions and Adventitial Remodeling in Deoxycorticosterone Acetate-Salt Hypertensive Rats
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醋酸脱氧皮质酮盐高血压大鼠的外膜成纤维细胞功能和外膜重塑需要血管周围脂肪组织来源的补体 3
DOI：
10.1161/atvbaha.110.215525
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发表时间：
2010-12-01
影响因子：
8.7
通讯作者：
Gao, Ping-Jin
中科院分区：
文献类型：
--
作者：
Ruan, Cheng-Chao;Zhu, Ding-Liang;Gao, Ping-Jin
研究血管周围脂肪组织（PVAT）衍生因子在体外和体内调节外膜成纤维细胞（AF）功能的作用。方法和结果-PVAT是血管的活性成分。PVAT释放的生物活性物质对血管功能具有调节作用。然而，其对血管性房颤的影响尚不清楚。PVAT条件培养基刺激AF迁移使用transwell技术，并通过α-平滑肌肌动蛋白诱导分化进行了评价。我们通过液相色谱-串联质谱法鉴定了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PVAT条件培养基诱导的AF迁移和分化。与PVAT条件培养基相似，C3重组蛋白刺激AF迁移和分化。我们证明了PVAT衍生的C3的作用是由c-Jun N-末端激酶途径介导的。此外，我们发现在血管周围的脂肪细胞的形态学变化和C3的表达增加PVAT是紧密相关的外膜增厚和肌成纤维细胞聚集周围PVAT在脱氧皮质酮醋酸盐hypertensive rats. Conclusion PVAT衍生C3刺激AF迁移和分化通过c-Jun N-末端激酶途径。PVAT衍生的C3可能有助于脱氧皮质酮醋酸盐高血压模型中的外膜重塑。（Arterioscler Thromb Vasc Biol.2010;30：2568-2574.）
Objective-To examine the role of perivascular adipose tissue (PVAT)-derived factors in the regulation of adventitial fibroblast (AF) function in vitro and in vivo.Methods and Results-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 alpha-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.Conclusion-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. (Arterioscler Thromb Vasc Biol. 2010;30:2568-2574.)