Rescue of Angiopoietin-2 Inhibits Proliferation of Lymphatic Malformation Endothelial Cells.

ABSTRACT: Cystic lymphatic malformations (LMs) are congenital anomalies characterized by the formation of dilated lymphatic channels that can infiltrate adjacent structures and cause significant morbidity. Somatic activating single nucleotide variants in PIK3CA have been identified in the majority of these lesions, yet the precise mechanisms underlying the role of these variants in LM progression remain unclear. Here, we investigated the role of Angiopoietin-2 (Ang2) downregulation downstream of pathogenic PIK3CA variants in the pathogenesis of LMs and delineated a novel inhibitory mechanism for autocrine Ang2 in the lymphatic vasculature. Transcriptomic profiling of patient-derived LM endothelial cells (LMECs) with PIK3CA variants revealed Ang2 as one of the most significantly downregulated genes.

SUBMITTER: Sun RW 

PROVIDER: S-EPMC12706717 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature