High importance
Sep 24, 2026
To investigate the pathogenesis of pulmonary vascular malformations (PVMs) in patients with single ventricle congenital heart disease and to identify shared mechanisms with hereditary hemorrhagic telangiectasia (HHT) arteriovenous malformations (AVMs).
Utilized a surgical rat model of Glenn circulation and performed single-cell RNA sequencing (scRNAseq) on lung samples to assess gene expression changes post-surgery. Examined the impact of dietary vitamin A intake on PVM severity in rats.
Identified significant changes in endothelial cell gene expression, with decreased all-trans retinoic acid (ATRA) signaling noted as a common feature between PVMs and HHT AVMs. A dietary deficiency in vitamin A exacerbated PVM shunting, while excess intake improved conditions.
The study's findings are based on a rat model, which may not fully replicate human conditions. Further research is needed to validate the results in human subjects and to explore the direct mechanisms of ATRA signaling in this context.
The findings provide new insights into shared pathological mechanisms between PVMs and HHT AVMs, proposing ATRA signaling as a novel therapeutic target which could facilitate more effective treatments for vascular malformations.
Pulmonary vascular malformations (PVMs) are vascular complications that universally develop in patients with single ventricle congenital heart disease after Glenn surgery, yet the pathogenesis of single ventricle PVMs remains unknown. Using a surgical rat model of Glenn circulation, single-cell RNA sequencing (scRNAseq) on whole lung samples identified dramatic endothelial cell (EC) gene expression changes post-surgery, including decreased all-trans retinoic acid (ATRA) signaling. Many gene expression differences (∼17% of all EC differentially expressed genes), including decreased ATRA signaling, were shared with 2 independent models of hereditary hemorrhagic telangiectasia arteriovenous malformations (AVMs). Subsequent dietary modification of vitamin A (Vit A) intake in rats, identified that dietary deficiency of Vit A increased PVM shunting severity, which was mitigated with excess dietary Vit A intake. Collectively, our study of post-Glenn PVMs identified shared patho-mechanisms with hereditary hemorrhagic telangiectasia AVMs, including decreased EC ATRA signaling, which is a novel potential target for treating AVMs.