Transmembrane protein 100 expression on endothelial cells vascularizing thrombi in chronic thromboembolic pulmonary hypertension modulates TGFβ1−ALK1 signaling during angiogenesis

Abstract

Endothelial cells within chronic pulmonary artery thrombi in CTEPH overexpress transmembrane protein 100 (TMEM100), an activin A receptor-like kinase 1 (ACVRL1 or ALK1) signaling-dependent gene, and TGFβ1 upregulated TMEM100 transcription in healthy lung ECs. TMEM100 permitted the TGFβ1-induced increase of ALK1, while repressing ALK5, and preventing ALK1–TMEM100 signaling impaired angiogenesis ex vivo. Our data indicate that TGFβ1–ALK1–TMEM100 signaling is active during CTEPH thrombus revascularization.