Key result
Vitamin A deficiency worsens PVM shunting via reduced ATRA signaling, while supplementation mitigates severity.
Why the study?
The pathogenesis of pulmonary vascular malformations in patients with single ventricle congenital heart disease after Glenn surgery remains unknown.
Does dietary vitamin A modification alter the severity of pulmonary vascular malformations in a surgical rat model of Glenn circulation?
Does dietary vitamin A modification alter the severity of pulmonary vascular malformations in a surgical rat model of Glenn circulation?
Decreased endothelial retinoic acid signaling is a shared pathomechanism in single ventricle pulmonary vascular malformations and hereditary hemorrhagic telangiectasia AVMs, highlighting it as a potential therapeutic target.
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.
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Rousseau et al. (2026) studied Pulmonary vascular malformations. Dietary modification of vitamin A was evaluated on PVM shunting severity. Dietary modification in a rat model showed that vitamin A deficiency increased PVM shunting severity, which was mitigated by excess vitamin A, implicating decreased ATRA signaling in pathogenesis.
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