Thbd, short for thrombomodulin, is a key component of the anticoagulant protein C-system. It acts at the endothelium and is involved in anti-inflammatory and barrier-stabilizing processes [2]. The protein C anticoagulant system is crucial for maintaining hemostatic balance [1].

In a population-based cohort study, rare qualifying Thbd variants were associated with an increased risk of venous thromboembolism (VTE), suggesting that these variants contribute to VTE development [1]. In ischemic stroke mouse models, inducible deletion of Thbd specifically in brain endothelial cells worsened stroke outcome, with decreased vessel diameters and impaired angiogenesis in the peri-infarct area, indicating that endogenous Thbd enhances vessel diameter and proliferation during ischemic stroke [2]. In the context of deep vein thrombosis (DVT) in mice, deletion of Brahma-related gene 1 (BRG1) in endothelial cells decreased DVT susceptibility, and BRG1 was found to epigenetically repress Thbd transcription [3].

In conclusion, Thbd is essential for maintaining hemostatic balance, anti-inflammatory and barrier-stabilizing processes. Gene knockout or conditional knockout mouse models have revealed its roles in diseases such as VTE, ischemic stroke, and DVT, providing insights into the underlying molecular mechanisms and potential therapeutic targets for these diseases.

References:

1. Manderstedt, Eric, Halldén, Christer, Lind-Halldén, Christina, Lotta, Luca A, Zöller, Bengt. 2022. Thrombomodulin (THBD) gene variants and thrombotic risk in a population-based cohort study. In Journal of thrombosis and haemostasis : JTH, 20, 929-935. doi:10.1111/jth.15630. https://pubmed.ncbi.nlm.nih.gov/34970867/

2. Wenzel, Jan, Spyropoulos, Dimitrios, Assmann, Julian Christopher, Isermann, Berend, Schwaninger, Markus. 2020. Endogenous THBD (Thrombomodulin) Mediates Angiogenesis in the Ischemic Brain-Brief Report. In Arteriosclerosis, thrombosis, and vascular biology, 40, 2837-2844. doi:10.1161/ATVBAHA.120.315061. https://pubmed.ncbi.nlm.nih.gov/33028093/

3. Wu, Teng, Kong, Ming, Xin, Xiao-Jun, Yang, Yu-Yu, Xiao, Ping-Xi. 2022. Epigenetic repression of THBD transcription by BRG1 contributes to deep vein thrombosis. In Thrombosis research, 219, 121-132. doi:10.1016/j.thromres.2022.09.015. https://pubmed.ncbi.nlm.nih.gov/36162255/