Laura Lorente-Herraiz, Angel M. Cuesta, Lucía Recio-Poveda, Luisa M. Botella, Virginia Albiñana
Centro de Investigaciones Biológicas Margarita Salas, CIB-CSIC. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER). Universidad Complutense de Madrid. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC).
Spain
International Journal of Molecular Sciences
Int J Mol Sci 2024; 25:
DOI: 10.3390/ijms25116163
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-β 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.
Category
Pulmonary Arteriovenous Malformations
Vascular Cell Biology and Mechanisms of Pulmonary Vascular Disease
Pulmonary Vascular Pathology
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
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Free PDF File or Full Text Article Available Through PubMed or DOI: Yes