Endoglina solublemecanismo de generación y función en células endoteliales y su efecto en el remodelado vascular

Resumo

Endoglin is a transmembrane homodimeric glycoprotein that plays a key role in angiogenesis and vascular remodeling, acting as a co-receptor of TGF-β family members in endothelial cells, and modulating the TGF-β signaling pathway through ALK-1 / ALK5. Mutations in endoglin gene are responsible for a rare disease known as Hereditary Hemorrhagic Telangiectasia (HHT), associated with recurrent bleedings and arteriovenous malformations. Endothelial damage in HHT has been postulated as one of the possible "second events" necessary for the formation of arteriovenous malformations. Under endothelial damage, the transcription factor Krüppel-Like-Factor 6 (KLF6) translocates into the cell nucleus to regulate a variety of target genes involved in endothelial repair and vascular remodeling, including components of the membrane TGF-β receptor family complex such as endoglin and ALK1. While most of endoglin studies have focused on the two membrane isoforms, the regulation and role of soluble endoglin are poorly understood. It is already known that membrane metalloproteinase 14 (MMP14) targets membrane endoglin in endothelial cells to release soluble endoglin to the medium. Soluble endoglin is involved in many cardiovascular, inflammatory and tumor pathologies, and it is known to have an antiangiogenic function. The fact that some of the treatments used for HHT have antiangiogenic properties raises the question of whether this soluble endoglin can modulate the arteriovenous malformations...