# Transmembrane Protein 100 Expression on Endothelial Cells Vascularizing Thrombi in Chronic Thromboembolic Pulmonary Hypertension Modulates TGFβ1−ALK1 Signaling During Angiogenesis

## TL;DR

A protein called TMEM100 helps control blood vessel growth in lung blood clots linked to a type of high blood pressure.

## Contribution

TMEM100's role in TGFβ1-ALK1 signaling during angiogenesis in CTEPH thrombi is newly identified.

## Key findings

- TMEM100 is overexpressed in endothelial cells of CTEPH thrombi and is regulated by TGFβ1.
- TMEM100 promotes ALK1 while repressing ALK5, influencing angiogenesis.
- Disrupting TMEM100-ALK1 signaling impairs blood vessel formation in experiments.

## 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.