2026-04-29T02:38:00Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/193652024-09-27T08:10:40Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Ruiz-Rodríguez, María Jesús author Oller, Jorge author Martínez-Martínez, Sara author Alarcón-Ruiz, Iván author Toral, Marta author Sun, Yilin author Colmenar, Ángel author Méndez-Olivares, María José author López-Maderuelo, Dolores author Kern, Christine B author Nistal, J Francisco author Evangelista, Arturo author Teixido-Tura, Gisela author Campanero, Miguel R author Redondo, Juan Miguel author 2024-01 Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening condition associated with Marfan syndrome (MFS), a disease caused by fibrillin-1 gene mutations. While various conditions causing TAAD exhibit aortic accumulation of the proteoglycans versican (Vcan) and aggrecan (Acan), it is unclear whether these ECM proteins are involved in aortic disease. Here, we find that Vcan, but not Acan, accumulated in Fbn1C1041G/+ aortas, a mouse model of MFS. Vcan haploinsufficiency protected MFS mice against aortic dilation, and its silencing reverted aortic disease by reducing Nos2 protein expression. Our results suggest that Acan is not an essential contributor to MFS aortopathy. We further demonstrate that Vcan triggers Akt activation and that pharmacological Akt pathway inhibition rapidly regresses aortic dilation and Nos2 expression in MFS mice. Analysis of aortic tissue from MFS human patients revealed accumulation of VCAN and elevated pAKT-S473 staining. Together, these findings reveal that Vcan plays a causative role in MFS aortic disease in vivo by inducing Nos2 via Akt activation and identify Akt signaling pathway components as candidate therapeutic targets. EMBO Mol Med. 2024 Jan;16(1):132-157. http://hdl.handle.net/20.500.12105/19365 38177536 10.1038/s44321-023-00009-7 1757-4684 EMBO molecular medicine Versican accumulation drives Nos2 induction and aortic disease in Marfan syndrome via Akt activation.