成纤维细胞激活蛋白-α (FAP) 是一种 II 型跨膜丝氨酸蛋白酶，与伤口愈合、癌症相关成纤维细胞和慢性纤维化疾病相关。然而，其在深静脉血栓形成（DVT）中的表达仍不清楚。因此，本研究调查了 DVT 中 FAP 的表达和定位。我们对 DVT 患者（n = 14）的抽吸血栓进行了病理分析，根据新鲜、细胞溶解和组织反应成分对血栓区域进行分类。组织反应包括内皮化和成纤维细胞反应。我们对FAP表达区域和细胞进行了免疫组织化学检查，最后分析了培养的真皮成纤维细胞中的FAP表达。所有抽吸的血栓均显示出三个血栓区域中至少两个的异质混合物。具体来说，83% 的抽吸血栓显示出新鲜且组织化的反应成分。 FAP 的免疫组织化学表达仅限于组织区域。双重免疫荧光染色显示血栓中的FAP主要表达于波形蛋白阳性或α-平滑肌肌动蛋白阳性的成纤维细胞中。一些 CD163 阳性巨噬细胞表达 FAP。在 0.1% 胎牛血清 (FBS) 下培养的低增殖活性成纤维细胞中，FAP mRNA 和蛋白质水平高于在 10% FBS 下培养的成纤维细胞。在补充氯高铁红素后，在 10% FBS 中培养的成纤维细胞显示 FAP mRNA 水平显着降低，但补充凝血酶后则不然。静脉血栓的异质成分表明人类 DVT 中存在多步骤血栓形成过程。此外，成纤维细胞或肌成纤维细胞可以在组织过程中表达FAP。 FAP 表达在增殖活性较低的成纤维细胞中可能较高。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

Fibroblast activation protein-α (FAP), a type-II transmembrane serine protease, is associated with wound healing, cancer-associated fibroblasts, and chronic fibrosing diseases. However, its expression in deep vein thrombosis (DVT) remains unclear. Therefore, this study investigated FAP expression and localization in DVT.We performed pathological analyses of the aspirated thrombi of patients with DVT (n = 14), classifying thrombotic areas in terms of fresh, cellular lysis, and organizing reaction components. The organizing reaction included endothelialization and fibroblastic reaction. We immunohistochemically examined FAP-expressed areas and cells, and finally analyzed FAP expression in cultured dermal fibroblasts.All the aspirated thrombi showed a heterogeneous mixture of at least two of the three thrombotic areas. Specifically, 83 % of aspirated thrombi showed fresh and organizing reaction components. Immunohistochemical expression of FAP was restricted to the organizing area. Double immunofluorescence staining showed that FAP in the thrombi was mainly expressed in vimentin-positive or α-smooth muscle actin-positive fibroblasts. Some CD163-positive macrophages expressed FAP. FAP mRNA and protein levels were higher in fibroblasts with low-proliferative activity cultured under 0.1 % fetal bovine serum (FBS) than that under 10 % FBS. Fibroblasts cultured in 10 % FBS showed a significant decrease in FAP mRNA levels following supplementation with hemin, but not with thrombin.The heterogeneous composition of venous thrombi suggests a multistep thrombus formation process in human DVT. Further, fibroblasts or myofibroblasts may express FAP during the organizing process. FAP expression may be higher in fibroblasts with low proliferative activity.Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.