{"database":"Pride","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Msf":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/EBK_JMR_aorta_MF_TMT_2_Fr3.msf","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/EBK_JMR_aorta_MF_TMT_1_Fr4.msf","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/EBK_JMR_aorta_MF_TMT_2.msf","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/EBK_JMR_aorta_MF_TMT_2_Fr4.msf","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/EBK_JMR_aorta_MF_TMT_2_Fr2.msf","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/EBK_JMR_aorta_MF_TMT_1.msf","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/EBK_JMR_aorta_MF_TMT_1_Fr3.msf","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/EBK_JMR_aorta_MF_TMT_2_Fr1.msf","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/EBK_JMR_aorta_MF_TMT_1_Fr1.msf","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/EBK_JMR_aorta_MF_TMT_1_Fr2.msf","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/EBK_JMR_aorta_MF_TMT_1_Fr5.msf","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/EBK_JMR_aorta_MF_TMT_2_Fr5.msf"],"Txt":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/checksum.txt"],"Raw":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/EBK_JMR_aorta_MF_TMT_1_Fr5.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/EBK_JMR_aorta_MF_TMT_1_Fr2.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/EBK_JMR_aorta_MF_TMT_2_Fr1.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/JMR_Mouse_Marfan_TMT_Fr1.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/EBK_JMR_aorta_MF_TMT_1_Fr1.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/JMR_Mouse_Marfan_TMT_Fr3_191002102636.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/JMR_Mouse_Marfan_TMT_Fr4_191003104527.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/JMR_Mouse_Marfan_TMT_Fr2.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/EBK_JMR_aorta_MF_TMT_2.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/EBK_JMR_aorta_MF_TMT_1_Fr3.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/EBK_JMR_aorta_MF_TMT_2_Fr2.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/JMR_Mouse_Marfan_TMT.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/EBK_JMR_aorta_MF_TMT_1_Fr4.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/EBK_JMR_aorta_MF_TMT_1.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/JMR_Mouse_Marfan_TMT_Fr3.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/JMR_Mouse_Marfan_TMT_Fr2_191001111830.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/JMR_Mouse_Marfan_TMT_Fr4.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD077940/EBK_JMR_aorta_MF_TMT_2_Fr3.raw"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"labhead_mail":["jvazquez@cnic.es"],"submitter":["Emilio Camafeita"],"technology_type":["Data-dependent acquisition","Mass Spectrometry","Bottom-up proteomics"],"disease":["Marfan Syndrome"],"software":["Not available"],"submitter_keywords":["Human","Mouse","Aortic tissue","Marfan syndrome"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD077940"],"tissue":["Aorta"],"sample_protocol":["High-throughput quantitative proteomics were performed by multiplexed isobaric labeling in aortic tissue from 12-week-old C57BL/6 MFS mice and WT littermates as controls. Each TMT 10-plex batch contained biological replicates from each experimental condition and an internal standard for TMT comparison. Peptides were TMT-labeled according to the manufacturer’s instructions and desalted on OASIS extraction cartridges. Labeled peptide samples were analyzed using a Proxeon Easy nano-flow HPLC system (Thermo Fisher Scientific; Waltham, USA) coupled via a nanoelectrospray ion source (Thermo Fisher Scientific) to either a Q-Exactive HF mass spectrometer (Termo Fisher Scientific) or an Orbitrap Fusion mass spectrometer (Thermo Fisher Scientific). Proteins were identified by searching against a mouse database (UniProtKB/Swiss-Prot and TrEMBL December_2020) supplemented with 116 CRAP proteins (Global Proteome Machine), totaling 50915 sequences."],"repository":["Pride"],"quantification_method":["Not available"],"modification":[""],"data_protocol":["Quantitative results were expressed as log2(Ai/C), where Ai is the intensity of the TMT reporter for the corresponding sample I, and C is the mean intensity of the TMT reporters from the controls or the mean value of the internal reference standards. Log2(ratios) from reporters were integrated to protein levels and statistical analysis was performed using iSanxot."],"omics_type":["Proteomics"],"labhead":["Jesús Vázquez"],"instrument_platform":[""],"submission_type":["PARTIAL"],"labhead_affiliation":["Cardiovascular Proteomics Laboratory Centro Nacional de Investigaciones Cardiovasculares (CNIC) Madrid, Spain"],"species":["Homo Sapiens (human)","Mus Musculus (mouse)"],"publication":["Not available"],"submitter_mail":["ecamafeita@cnic.es"],"submitter_affiliation":["Proteomics Unit\nVascular Pathophysiology Area\nCNIC"],"submitter_country":["Spain"],"additional_accession":[]},"is_claimable":false,"name":"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.","dates":{"publication":"2026-06-02","submission":"2026-05-02"},"accession":"PXD077940","cross_references":{"TAXONOMY":["NEWT:6945","NEWT:3555","NEWT:2","NEWT:157546","NEWT:35554","NEWT:38942","NEWT:307972","NEWT:32046","NEWT:544496","NEWT:2042546","NEWT:45351","NEWT:43179","NEWT:4513","NEWT:5722","NEWT:376741","NEWT:55153","NCBITaxon:10407","NEWT:1736309","NEWT:1211601","NEWT:876138","NEWT:237561","NEWT:5833","NEWT:6928","NEWT:10036","NEWT:36745","NEWT:1351","NEWT:1438992","NEWT:2649997","NEWT:272563","NEWT:224326","NCBITaxon:79857","NEWT:1096976","NEWT:95648","NEWT:3885","NEWT:3888","NEWT:1589","NEWT:135622","NEWT:6915","NEWT:3649","NEWT:101510","NEWT:3880","NEWT:272559","NEWT:3641","NEWT:383379","NEWT:10029","NEWT:1000589","NEWT:85962","NEWT:317447","NEWT:7955","NEWT:7959","NEWT:2261","NEWT:31156","NEWT:4565","NEWT:1264690","NEWT:515619","NEWT:192875","NEWT:34305","NEWT:59729","NCBITaxon:183674","NEWT:224308","NEWT:84645","NEWT:626528","NEWT:139927","NEWT:4558","NEWT:209285","NEWT:1283","NEWT:931281","NEWT:4550","NEWT:1000561","NEWT:197","NCBITaxon:79824","NEWT:4787","NCBITaxon:4563","NEWT:5755","NEWT:44689","NEWT:3218","NEWT:5759","NEWT:1736231","NEWT:1270","NEWT:2242","NEWT:4784","NEWT:11320","NEWT:360106","NEWT:287","NEWT:10117","NEWT:10239","NEWT:10116","NEWT:1280","NEWT:1735272","NEWT:83334","NEWT:83332","NEWT:44685","NEWT:317513","NEWT:1148","NEWT:580240","NEWT:294128","NEWT:11676","NEWT:55571","NEWT:100226","NEWT:4530","NEWT:4896","NEWT:75058","NEWT:13616","NEWT:1094343","NEWT:296543","NEWT:1773","NEWT:1895","NEWT:1182590","NEWT:935293","NEWT:64152","NEWT:4924","NEWT:749200","NEWT:990346","NEWT:145953","NEWT:257309","NEWT:100816","NEWT:263","NEWT:230741","NEWT:52283","NEWT:284812","NCBITaxon:1313","NEWT:43330","NEWT:408169","NEWT:44544","NEWT:4911","NEWT:645463","NEWT:3702","NEWT:129249","NEWT:990119","NEWT:408172","NEWT:408170","NEWT:493760","NEWT:260710","NEWT:257313","NEWT:400772","NEWT:3708","NEWT:128161","NEWT:332648","NEWT:106592","NEWT:536231","NEWT:1432138","NEWT:10312","NEWT:1424507","NCBITaxon:1773","NEWT:9598","NEWT:8030","NEWT:1639","NEWT:188229","NEWT:3818","NEWT:480","NEWT:4909","NEWT:67767","NEWT:432359","NEWT:46835","NEWT:2711","NEWT:376686","NEWT:95486","NEWT:9103","NEWT:29159","NEWT:10306","NCBITaxon:2759","NEWT:1233435","NEWT:8022","NEWT:145943","NCBITaxon:4932","NEWT:595536","NEWT:240906","NEWT:593117","NEWT:3635","NEWT:5811","NEWT:235443","NEWT:411483","NEWT:884019","NEWT:198215","NEWT:411490","NEWT:983964","NEWT:169963","NEWT:499175","NEWT:476272","NEWT:3747","NEWT:367830","NEWT:178616","NEWT:410289","NEWT:373153","NEWT:352472","NEWT:360094","NEWT:470","NEWT:1313","NEWT:411469","NEWT:84023","NEWT:559292","NCBITaxon:5811","NEWT:411464","NEWT:411460","NEWT:2762","NEWT:1174673","NEWT:562","NEWT:411470","NEWT:33952","NEWT:2094720","NCBITaxon:2697049","NEWT:28038","NEWT:1423","NEWT:4932","NEWT:3603","NEWT:2759","NEWT:3847","NEWT:327159","NEWT:178876","NEWT:327160","NEWT:573","NEWT:9031","NEWT:7091","NEWT:241368","NEWT:42528","NEWT:190802","NEWT:9778","NEWT:150475","NEWT:9417","NEWT:7111","NEWT:347515","NEWT:1216979","NEWT:5180","NEWT:256737","NEWT:115104","NEWT:1081927","NEWT:1238993","NEWT:67825","NEWT:185579","NEWT:13076","NEWT:1249668","NEWT:317","NEWT:7227","NEWT:7469","NEWT:885318","NEWT:9402","NEWT:415540","NEWT:4081","NEWT:554","NEWT:98334","NEWT:426428","NEWT:7574","NEWT:7215","NEWT:575412","NEWT:29204","NEWT:2172103","NEWT:507601","NCBITaxon:6157","NEWT:746360","NEWT:6239","NEWT:470150","NEWT:216257","NEWT:9986","NEWT:4054","NEWT:73239","NEWT:226186","NEWT:1268063","NEWT:8782","NEWT:1263854","NEWT:435590","NEWT:1902","NEWT:160488","NEWT:28104","NEWT:1908","NCBITaxon:2","NEWT:985076","NEWT:1215323","NEWT:52641","NEWT:7038","NEWT:6192","NEWT:28532","NCBITaxon:38727","NEWT:2829","NEWT:216599","NEWT:216595","NEWT:243230","NEWT:8355","NEWT:9685","NEWT:7029","NEWT:1080772","NEWT:1283300","NEWT:6183","NEWT:6063","NEWT:334747","NEWT:61235","NEWT:6289","NEWT:436486","NEWT:6287","NEWT:300641","NEWT:727","NEWT:9796","NEWT:725","NEWT:170187","NEWT:260707","NCBITaxon:6191","NEWT:1836","NEWT:185431","NEWT:29760","NEWT:260704","NEWT:703612","NEWT:260705","NEWT:80863","NEWT:2697049","NEWT:1216981","NCBITaxon:6073","NEWT:884204","NEWT:6279","NEWT:1123869","NEWT:9544","NEWT:7370","NEWT:83906","NEWT:607699","NEWT:6282","NEWT:208964","NEWT:1134506","NEWT:575584","NEWT:38783","NEWT:8727","NEWT:4006","NEWT:8726","NEWT:6426","NEWT:6669","NEWT:10090","NEWT:4120","NEWT:51515","NEWT:5693","NEWT:8724","NEWT:51511","NEWT:92867","NEWT:8723","NEWT:5334","NEWT:37334","NEWT:382352","NCBITaxon:10359","NEWT:242619","NEWT:632957","NEWT:373995","NEWT:5689","NEWT:544404","NEWT:9925","NEWT:8839","NEWT:4232","NEWT:2758385","NEWT:4113","NEWT:837","NEWT:11298","NEWT:171101","NEWT:714","NEWT:421932","NEWT:196627","NEWT:5691","NEWT:48479","NEWT:627025","NEWT:1097677","NEWT:61674","NEWT:1117957","NEWT:9913","NEWT:4100","NEWT:1076","NEWT:6763","NEWT:803","NEWT:29722","NEWT:380394","NEWT:1692259","NEWT: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