Expression of fibroblast activation protein-α in human deep vein thrombosis

• Published in: Thrombosis research Vol. 241; p. 109075
• Main Authors: Oguri, Nobuyuki, Gi, Toshihiro, Nakamura, Eriko, Furukoji, Eiji, Goto, Hiroki, Maekawa, Kazunari, Tsuji, Atsushi B., Nishii, Ryuichi, Aman, Murasaki, Moriguchi-Goto, Sayaka, Sakae, Tatefumi, Azuma, Minako, Yamashita, Atsushi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.09.2024
• Subjects: Adult; Aged; Cells, Cultured; Deep vein thrombosis; Endopeptidases - metabolism; Female; Fibroblast; Fibroblast activation protein-α; Fibroblasts - metabolism; Fibroblasts - pathology; Gelatinases - metabolism; Hematology, Oncology, and Palliative Medicine; Humans; Male; Membrane Proteins - metabolism; Middle Aged; Organization; Podoplanin; Serine Endopeptidases - metabolism; Venous Thrombosis - metabolism; Venous Thrombosis - pathology; Young Adult; α2-antiplasmin; Deep vein thrombosis; α2-antiplasmin; Fibroblast activation protein-α; Organization; Fibroblast; Podoplanin
• ISSN: 0049-3848; 1879-2472; 1879-2472
• DOI: 10.1016/j.thromres.2024.109075

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. [Display omitted] •Human deep vein thrombosis (DVT) has heterogenous fresh, lytic, and organizing areas•Fibroblasts in DVT organizing area express fibroblast activated protein-α (FAP)•FAP expression is upregulated in fibroblasts with low proliferative activity