Prideapplication/xmlftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD073197/D4_rerun.msfftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD073197/D5_rerun.msfftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD073197/D6_rerun.msfftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD073197/D1_rerun.msfftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD073197/D3_rerun.msfftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD073197/D2_rerun.msfftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD073197/checksum.txtftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD073197/D3_rerun.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD073197/D2_rerun.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD073197/D1_rerun.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD073197/D5_rerun.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD073197/D6_rerun.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD073197/D4_rerun.rawprimaryOK200hkim3@augusta.eduWenbo ZhiMass SpectrometryBottom-up proteomicsLiverSoluble epoxide hydrolaseAbdominal aortic aneurysmAngiotensin iiCalcium chloridehttps://www.ebi.ac.uk/pride/archive/projects/PXD073197Whole aortas from either sham- or CaCl2-treated mice were harvested 7 days after laparotomy and transferred to a 48-well plate with 500 μl of serum-free DMEM media. The conditioned media was collected after 12 hr incubation, centrifuged at 1000 g for 10 min, filtered through a Nalgene 0.2 μm pore vacuum filter, and concentrated using a 10 kDa MWCO Amicon Ultra-15 centrifugal filter (MiliporeSigma) operating at 1500 g for 30 min with 50 mM ammonium bicarbonate buffer until the final concentration was 2 mg/ml.PrideRaw data were analyzed using Proteome Discoverer (v1.4, Thermo Scientific) and searched against the UniProt mouse protein database. Peptide-spectrum match (PSM) values, a total number of identified peptide spectra matched for the protein, were log-transformed to normalize the dataset. LIMMA package on R was used to compare protein levels in conditioned media of the aorta obtained from sham- versus CaCl2-treated mice, and p478 values were adjusted using FDR (false discovery rate), with significance set at an adjusted p-value <0.05. The annotated genes were used as input for functional enrichment analysis, which was performed using the Gene Ontology (GO) terms.ProteomicsKim, Ha WonVascular Biology Center, Augusta UniversityPARTIALMus Musculus (mouse)41772184 Kim DS, Horimatsu T, Ogbi M, Goo B, Shi H, Veerapaneni P, Chouhaita R, Cyriac N, Moses M, Prasad R, Cave S, Benson TW, Harb R, Aboud G, Sellers HG, Shivers M, Haigh S, Fulton DJ, Csányi G, Huo Y, Long X, Coffey P, Lee R, Guha A, Zhi W, Young L, Zeldin DC, Hwang SH, Hammock BD, Weintraub NL, Kim HW. Soluble epoxide hydrolase in the liver orchestrates abdominal aortic aneurysm formation in mice. Commun Biol. 2026 10.1038/s42003-026-09765-xwzhi@augusta.eduAugusta UniversityUnited StatesThe liver plays an important role in cardiovascular disease by amplifying systemic inflammation, while the underlying mechanisms remain to be defined. Soluble epoxide hydrolase (sEH) is a pro-inflammatory enzyme, and pharmacological inhibition of sEH was shown to protect against various inflammatory diseases. In this study, we have identified a novel role of the liver, through expression of sEH, in the pathogenesis of abdominal aortic aneurysm (AAA). sEH expression and activity were markedly higher in mouse liver compared with aorta and further increased in the context of AAA. Pharmacological inhibition or hepatocyte-specific disruption of sEH prevented AAA formation in two animal models of AAA (angiotensin II infusion and aortic calcium chloride application in male mice), concomitant with reduced expression of complement C3 and serum amyloid A, liver-derived inflammatory factors causally linked to AAA formation. Interestingly, data from co-incubation of liver ex vivo with aorta identified galectin-3 secreted from the aneurysm-prone aorta that activates sEH in the liver. We also determined 12,13-dihydroxyoctadecenoic acid (DiHOME) and various circulating pro-inflammatory cytokines as a downstream mechanism potentially associated with hepatic sEH in the context of AAA. These novel findings provide direct evidence that bidirectional crosstalk between aorta and liver contributes to AAA via hepatic sEH.Soluble epoxide hydrolase in the liver orchestrates abdominal aortic aneurysm formation in mice.Kim David S DS, Horimatsu Tetsuo T, Ogbi Mourad M, Goo Brandee B, Shi Hong H, Veerapaneni Praneet P, Chouhaita Ronnie R, Cyriac Nicole N, Moses Mary M, Prasad Rosaria R, Cave Stephen S, Benson Tyler W TW, Harb Ragheb R, Aboud Ghaith G, Sellers Hunter G HG, Shivers Mitchell M, Haigh Stephen S, Fulton David J DJ, Csányi Gábor G, Huo Yuqing Y, Long Xiaochun X, Coffey Philip P, Lee Richard R, Guha Avirup A, Zhi Wenbo W, Young Lufei L, Zeldin Darryl C DC, Hwang Sung Hee SH, Hammock Bruce D BD, Weintraub Neal L NL, Kim Ha Won HWfalseSoluble epoxide hydrolase in the liver orchestrates abdominal aortic aneurysm formationThe liver plays an important role in cardiovascular disease by amplifying systemic inflammation, while the underlying mechanisms remain to be defined. Soluble epoxide hydrolase (sEH) is a pro-inflammatory enzyme and pharmacological inhibition of sEH was shown to protect against various inflammatory diseases. In this study, we have identified a novel role of the liver, through expression of sEH, in the pathogenesis of abdominal aortic aneurysm (AAA). sEH expression and activity were markedly higher in mouse liver compared with aorta and further increased in the context of AAA. Pharmacological inhibition or hepatocyte-specific disruption of sEH prevented AAA formation in two animal models of AAA (systemic angiotensin II infusion and local aortic calcium chloride application), concomitant with reduced expression of complement C3 and serum amyloid A, liver-derived inflammatory factors causally linked to AAA formation. Interestingly, data from co-incubation of liver ex vivo with aorta identified galectin-3 secreted from the aneurysm-prone aorta that activate sEH in the liver. We also determined 12,13- dihydroxyoctadecenoic acid (DiHOME) and various circulating pro-inflammatory cytokines as a downstream mechanism potentially associated with hepatic sEH in the context of AAA. These novel findings provide direct evidence that bidirectional crosstalk between aorta and liver contributes to AAA via hepatic sEH.2026-04-072026-01-18PXD073197NEWT:3555NEWT:71647NEWT:35554NEWT:32046NEWT:544496NEWT:2042546NEWT:32049NEWT:1392696NEWT:259447NEWT:45351NEWT:445974NEWT:43179NEWT:180454NEWT:5722NCBITaxon:1280NEWT:1129NEWT:309807NEWT:55153NEWT:309800NEWT:281395NEWT:1211601NEWT:876138NEWT:44271NEWT:10036NEWT:1590NEWT:498019NEWT:1351NEWT:1438992NEWT:1352NEWT:2649997NEWT:1147161NEWT:263737NEWT:224326NEWT:1333499NCBITaxon:79857NEWT:1096976NEWT:95648NEWT:1589NEWT:135622NEWT:1349NEWT:96731NEWT:383379NEWT:10029NEWT:913645NEWT:44491NEWT:556484NEWT:317447NEWT:4688NEWT:7955NEWT:7959NEWT:2261NEWT:31156NEWT:3112NEWT:4442NEWT:192875NEWT:1214915NEWT:12637NEWT:59729NEWT:2164133NEWT:108061NEWT:1316931NEWT:224308NEWT:3347NEWT:511145NEWT:931281NEWT:658457NEWT:1310161NEWT:77133NEWT:295358NEWT:145481NCBITaxon:79824NCBITaxon:4563NEWT:5755NEWT:44689NEWT:44447NEWT:5759NEWT:1736231NEWT:5518NEWT:1392NEWT:498217NEWT:2242NEWT:11320NEWT:286NEWT:391619NEWT:246196NEWT:287NEWT:246197NEWT:633149NEWT:10239NEWT:44685NEWT:161934NEWT:1148NEWT:5508NEWT:5507NEWT:410661NEWT:55571NEWT:35500NEWT:1140NCBITaxon:2157NEWT:1143NEWT:4896NEWT:1390NEWT:11557NEWT:1094343NEWT:1336795NEWT:644042NEWT:294NEWT:1773NEWT:1182590NEWT:3712NEWT:82380NEWT:935293NEWT:375146NEWT:118698NEWT:263NEWT:118696NEWT:52283NEWT:284812NEWT:8175NEWT:43330NEWT:1603293NEWT:408169NEWT:44664NEWT:47946NEWT:3702NEWT:243277NEWT:7067NEWT:118694NEWT:2850NEWT:118691NEWT:33548NEWT:274NEWT:408172NEWT:408170NEWT:96794NEWT:3708NEWT:332648NEWT:44670NEWT:536231NEWT:376219NEWT:1436733NEWT:460519NEWT:1247411NEWT:572307NEWT:1432138NEWT:1424507NEWT:1194599NEWT:272844NEWT:9483NEWT:333760NEWT:1513458NCBITaxon:40559NEWT:84588NEWT:1679718NEWT:480NEWT:67767NEWT:46835NEWT:109757NEWT:582580NEWT:300852NEWT:1502NEWT:376686NEWT:95486NEWT:508771NEWT:1883446NEWT:253NCBITaxon:2759NEWT:1233435NEWT:93061NEWT:93062NCBITaxon:4932NEWT:644223NEWT:235443NEWT:108458NEWT:272623NEWT:272624NEWT:320637NEWT:983964NEWT:118499NEWT:32644NEWT:527796NEWT:499175NEWT:109779NEWT:3745NEWT:1715989NCBITaxon:4751NEWT:476272NEWT:3747NEWT:195051NEWT:3988NEWT:1255228NEWT:649908NEWT:410289NEWT:373153NEWT:352472NEWT:1071661NEWT:360094NEWT:470NEWT:41364NEWT:1313NEWT:39491NCBITaxon:5811NEWT:29491NEWT:2014887NEWT:33952NEWT:261756NEWT:571256NEWT:40483NEWT:272634NEWT:9031NEWT:1872122NEWT:7091NEWT:141262NEWT:108931NEWT:1055524NEWT:4087NEWT:9778NEWT:306NEWT:150475NEWT:303NEWT:267872NEWT:7111NEWT:347515NEWT:9534NEWT:5180NEWT:256737NEWT:4090NEWT:4092NEWT:9541NEWT:8694NEWT:4093NEWT:4096NEWT:8692NEWT:185579NEWT:941442NEWT:13076NEWT:1226408NEWT:7108NEWT:40479NEWT:4076NEWT:317NEWT:1006581NEWT:885318NEWT:39488NEWT:550NEWT:4081NEWT:273068NEWT:554NEWT:98334NEWT:451516NEWT:4084NEWT:36185NEWT:1225786NEWT:7574NEWT:1715256NEWT:30640NEWT:575412NEWT:929793NEWT:29204NEWT:28112NEWT:114155NEWT:6494NEWT:6491NEWT:507601NEWT:186441NEWT:643680NEWT:214092NCBITaxon:6157NEWT:6239NEWT:162425NEWT:216257NEWT:102169NEWT:9986NEWT:4054NEWT:8654NEWT:8658NEWT:1268063NEWT:8655NEWT:1263854NEWT:118503NEWT:2059687NEWT:160488NEWT:28104NEWT:407821NCBITaxon:2NEWT:985076NEWT:1215323NEWT:986NEWT:52641NEWT:7159NEWT:28532NEWT:353152NEWT:8496NEWT:27448NEWT:40674NEWT:1194669NEWT:243230NEWT:1080772NEWT:519NEWT:8479NEWT:8485NEWT:6063NEWT:49240NEWT:104395NEWT:6289NEWT:6287NEWT:300641NEWT:727NEWT:9796NEWT:725NEWT:469008NEWT:256318NEWT:9321NEWT:206411NCBITaxon:6191NEWT:596153NEWT:229533NEWT:1836NEWT:80863NEWT:105231NEWT:52638NEWT:57075NEWT:4097NEWT:8697NEWT:8695NEWT:884204NEWT:9785NEWT:6279NEWT:1123869NEWT:9544NEWT:7370NEWT:83906NCBITaxon:780NCBITaxon:1502NEWT:6282NEWT:1134506NEWT:38783NEWT:4006NEWT:6426NCBITaxon:5476NEWT:6669NEWT:9935NEWT:89453NEWT:287889NEWT:51515NEWT:588596NEWT:51511NEWT:8845NEWT:92867NEWT:92866NEWT:5334NEWT:51750NEWT:202950NEWT:382352NEWT:413071NCBITaxon:714NEWT:632957NEWT:9925NEWT:89462NCBITaxon:9606NEWT:8839NEWT:90690NEWT:4232NEWT:2758385NEWT:11298NEWT:171101NEWT:714NEWT:421932NEWT:312017NEWT:196627NEWT:200308NEWT:200302NEWT:870435NEWT:284593NEWT:100392NEWT:5315NEWT:9913NEWT:265872NEWT:105841NEWT:337330NEWT:2666255NEWT:2285NEWT:999810NCBITaxon:5693NEWT:1392998NEWT:380394NEWT:981087NEWT:180066NEWT:226900NEWT:231490NEWT:430615NEWT:326423NEWT:452467NEWT:198822NEWT:36111NEWT:326424NEWT:1416333NEWT:1678078NEWT:749906NEWT:418985NEWT:1817808NEWT:749907NEWT:145263NEWT:694569NEWT:27606NEWT:9739NEWT:59202NEWT:9975NEWT:8643NEWT:51953NEWT:3197NEWT:860688NEWT:13443NEWT:8644NEWT:36329NEWT:62615NCBITaxon:3044782NEWT:160235NEWT:72407NEWT:8639NEWT:349741NEWT:409859NEWT:157295NEWT:2096NEWT:192222NEWT:9721NEWT:137221NEWT:9963NEWT:1617910NEWT:565050NEWT:409860NEWT:2785785NEWT:411901NEWT:8626NEWT:105884NCBITaxon:9615NEWT:8621NEWT:58334NEWT:1193501NEWT:58331NEWT:6689NEWT:8624NEWT:5116NEWT:8623NEWT:298315NEWT:8618NEWT:70448NEWT:698936NEWT:9940NEWT:3168NEWT:521001NEWT:192011NEWT:1813887NEWT:118702NEWT:118700NEWT:224911NEWT:118705NCBITaxon:11552NEWT:6945NEWT:184922NEWT:6703NEWT:2104NEWT:2NEWT:157546NEWT:474186NEWT:38942NEWT:1493NEWT:307972NEWT:1496NEWT:2102NEWT:660469NEWT:45474NEWT:1590841NEWT:4513NEWT:1247NEWT:70667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