肿瘤内皮标志物 1 (TEM1) 是一种活化的间充质细胞标志物，与组织重塑和修复有关。在此，我们研究了 TEM1 在腹主动脉瘤 (AAA) 中的作用和治疗意义，腹主动脉瘤是一种潜在危及生命的主动脉疾病，其特征是血管炎症和基质周转。人类 AAA 的表征显示，TEM1 表达增加主要源自内侧血管平滑肌细胞 (VSMC) 和外膜成纤维细胞。生物信息学分析证明了表达 TEM1 的 VSMC 与成纤维细胞和胶原蛋白基因表达之间的关联。一致地，在 CaCl2 诱导小鼠 AAA 形成过程中，VSMC 和成纤维细胞表达的胶原蛋白含量和 TEM1 增加。 VSMC 和成纤维细胞中的 TEM1 沉默抑制了转化生长因子-β1 诱导的表型变化、SMAD2 磷酸化和 COL1A1 基因表达。此外，Tem1 缺乏会减少小鼠体内胶原蛋白的合成，并加剧 CaCl2 诱导的 AAA 形成，但不会干扰弹性蛋白破坏和炎症反应。相比之下，rTEM1 通过 VSMC 和成纤维细胞中 SMAD2 磷酸化促进表型变化和 COL1A1 基因表达。 rTEM1 治疗增强了胶原蛋白合成，减少了弹性蛋白断裂，并抑制了 CaCl2 诱导和血管紧张素 II 注入的 AAA 形成。总之，驻留基质细胞中的 TEM1 调节胶原蛋白合成，以抵消 AAA 形成过程中的主动脉壁衰竭。 rTEM1 治疗恢复的基质完整性可能具有针对 AAA 的治疗潜力。© 作者。

Tumor endothelial marker 1 (TEM1), an activated mesenchymal cell marker, is implicated in tissue remodeling and repair. Herein, we investigated the role and therapeutic implications of TEM1 in abdominal aortic aneurysm (AAA), a potentially life-threatening aortic disease characterized by vascular inflammation and matrix turnover. Characterization of human AAA revealed increased TEM1 expression derived mainly from medial vascular smooth muscle cells (VSMCs) and adventitial fibroblasts. Bioinformatics analysis demonstrated the association between TEM1-expressing VSMCs and fibroblasts and collagen gene expression. Consistently, collagen content and TEM1 expressed by VSMCs and fibroblasts were increased during CaCl2-induced AAA formation in mice. TEM1 silencing in VSMCs and fibroblasts inhibited transforming growth factor-β1-induced phenotypic change, SMAD2 phosphorylation, and COL1A1 gene expression. Also, Tem1 deficiency reduced collagen synthesis and exacerbated CaCl2-induced AAA formation in mice without disturbing elastin destruction and inflammatory responses. In contrast, rTEM1 promoted phenotypic change and COL1A1 gene expression through SMAD2 phosphorylation in VSMCs and fibroblasts. Treatment with rTEM1 enhanced collagen synthesis, attenuated elastin fragmentation, and inhibited CaCl2-induced and angiotensin II-infused AAA formation. In summary, TEM1 in resident stromal cells regulates collagen synthesis to counteract aortic wall failure during AAA formation. Matrix integrity restored by rTEM1 treatment may hold therapeutic potential against AAA.© The author(s).