Endothelial-to-Mesenchymal Transition in an Hereditary Hemorrhagic Telangiectasia-like Pediatric Case of Multiple Pulmonary Arteriovenous Malformations.
Int J Mol Sci
; 25(11)2024 Jun 03.
Article
in En
| MEDLINE
| ID: mdl-38892351
ABSTRACT
Pulmonary arteriovenous malformations (PAVMs) are vascular anomalies resulting in abnormal connections between pulmonary arteries and veins. In 80% of cases, PAVMs are present from birth, but clinical manifestations are rarely seen in childhood. These congenital malformations are typically associated with Hereditary Hemorrhagic Telangiectasia (HHT), a rare disease that affects 1 in 5000/8000 individuals. HHT disease is frequently caused by mutations in genes involved in the TGF-ß pathway. However, approximately 15% of patients do not have a genetic diagnosis and, among the genetically diagnosed, more than 33% do not meet the Curaçao criteria. This makes clinical diagnosis even more challenging in the pediatric age group. Here, we introduce an 8-year-old patient bearing a severe phenotype of multiple diffuse PAVMs caused by an unknown mutation which ended in lung transplantation. Phenotypically, the case under study follows a molecular pattern which is HHT-like. Therefore, molecular- biological and cellular-functional analyses have been performed in primary endothelial cells (ECs) isolated from the explanted lung. The findings revealed a loss of functionality in lung endothelial tissue and a stimulation of endothelial-to-mesenchymal transition. Understanding the molecular basis of this transition could potentially offer new therapeutic strategies to delay lung transplantation in severe cases.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pulmonary Artery
/
Pulmonary Veins
/
Telangiectasia, Hereditary Hemorrhagic
/
Endothelial Cells
Limits:
Child
/
Female
/
Humans
/
Male
Language:
En
Journal:
Int J Mol Sci
Year:
2024
Type:
Article
Affiliation country:
Spain