PXD077940

PXD077940 is an original dataset announced via ProteomeXchange.

Title	Marfan mouse and human aortic tissue
Description	Thoracic aortic aneurysms and dissections (TAAD), as occur in Marfan syndrome (MFS), currently lack a cure. Our previous studies revealed that overactivation of the AKT-NO signaling pathway mediates aortic disease in MFS. However, the mechanisms upstream of AKT activation remained poorly understood. Here we identify the Fibronectin-αVβ3-PI3K-PIP3-PDK1-ILK cascade as a critical mediator of AKT-NOS2 upregulation and aortic disease in MFS. We show that fibronectin (FN) accumulates in the walls of human and mouse MFS aortas. Disrupting FN multimerization inhibits AKT activation and NOS2 induction in vascular smooth muscle cells (VSMCs), prevents aortic contractility dysregulation, and reverses aortic dilation in MFS mice. Mechanistically, both human and mouse MFS aortas exhibit αVβ3 and ILK upregulation. Pharmacological inhibition of αVβ3, PI3K, PDK1, and ILK, or their recruitment to the plasma membrane by PIP3, prevents FN-induced AKT activation and NOS2 upregulation in VMSCs and aortic contractility dysregulation. Furthermore, ILK inhibition or aortic silencing reverses aortic disease, while its deletion in smooth muscle cells prevents aortic growth in MFS mice. These findings establish the most thoroughly characterized pathway implicated in MFS to date and suggest a causative role for the FN-αVβ3-PI3K-PIP3-PDK1-ILK-AKT-NOS2 cascade in human TAAD, highlighting its components as potential targets for therapeutic intervention.
HostingRepository	PRIDE
AnnounceDate	2026-06-02
AnnouncementXML	Submission_2026-06-02_08:26:05.041.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Emilio Camafeita
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2026-05-01 22:39:00	ID requested
⏵ 1	2026-06-02 08:26:05	announced

Dataset with its publication pending

submitter keyword: human, aortic tissue, mouse,Marfan syndrome

Jesús Vázquez
contact affiliation	Cardiovascular Proteomics Laboratory Centro Nacional de Investigaciones Cardiovasculares (CNIC) Madrid, Spain
contact email	jvazquez@cnic.es
lab head
Emilio Camafeita
contact affiliation	Proteomics Unit Vascular Pathophysiology Area CNIC
contact email	ecamafeita@cnic.es
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940

PRIDE project URI

• PRIDE
  1. PXD077940
     1. Label: PRIDE project
     2. Name: Marfan mouse and human aortic tissue