{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sedighi S"],"funding":["NHLBI NIH HHS"],"pagination":["36082-36097"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12371761"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(32)"],"pubmed_abstract":["Heart failure (HF) is a complex condition. Among altered signal transduction pathways associated with HF pathogenesis, the stress-activated p38 mitogen-activated protein kinase (Mapk) pathway has attracted attention for its role in HF progression and cardiac hypertrophy. However, the mechanisms by which p38-Mapk influences HF remain unclear. Addressing knowledge gaps may provide insight into why p38 inhibition has yielded inconsistent outcomes in clinical trials. Here, we investigate the effects of p38-Mapk inhibition via SB203580 on cardiac remodeling in a guinea pig model of HF and sudden cardiac death. Using an HF model with ascending aortic constriction and daily isoproterenol (ACi) administration, we assessed three groups: sham-operated controls, untreated ACi, and ACi treated with SB203580 (ACiSB). Cardiac function was evaluated by M-mode echocardiography. Proteome and phosphoproteome profiles were analyzed using multiplexed Tandem Mass Tag labeling and LC-MS/MS. Our findings demonstrate that SB203580 treatment protects against cardiac dysfunction in HF. Proteomic data indicate that SB203580 exerts broad protection of the cardiac phosphoproteome, inhibiting maladaptive p38-dependent phosphorylation, extending to Pka and Ampk networks, ultimately protecting the phosphorylation status of critical myofibrillar and Ca<sup>2+</sup>-handling proteins. Though SB203580 had a limited impact on widespread protein changes in HF, its biosignature revealed preserved mitochondrial energetics and reduced oxidative and inflammatory stress."],"journal":["ACS omega"],"pubmed_title":["Inhibition of Cardiac p38 Highlights the Role of the Phosphoproteome in Heart Failure Progression."],"pmcid":["PMC12371761"],"funding_grant_id":["R01 HL134821","R01 HL164478"],"pubmed_authors":["O'Rourke B","Sedighi S","O'Meally R","Liu T","Cole RN","Foster DB"],"additional_accession":[]},"is_claimable":false,"name":"Inhibition of Cardiac p38 Highlights the Role of the Phosphoproteome in Heart Failure Progression.","description":"Heart failure (HF) is a complex condition. Among altered signal transduction pathways associated with HF pathogenesis, the stress-activated p38 mitogen-activated protein kinase (Mapk) pathway has attracted attention for its role in HF progression and cardiac hypertrophy. However, the mechanisms by which p38-Mapk influences HF remain unclear. Addressing knowledge gaps may provide insight into why p38 inhibition has yielded inconsistent outcomes in clinical trials. Here, we investigate the effects of p38-Mapk inhibition via SB203580 on cardiac remodeling in a guinea pig model of HF and sudden cardiac death. Using an HF model with ascending aortic constriction and daily isoproterenol (ACi) administration, we assessed three groups: sham-operated controls, untreated ACi, and ACi treated with SB203580 (ACiSB). Cardiac function was evaluated by M-mode echocardiography. Proteome and phosphoproteome profiles were analyzed using multiplexed Tandem Mass Tag labeling and LC-MS/MS. Our findings demonstrate that SB203580 treatment protects against cardiac dysfunction in HF. Proteomic data indicate that SB203580 exerts broad protection of the cardiac phosphoproteome, inhibiting maladaptive p38-dependent phosphorylation, extending to Pka and Ampk networks, ultimately protecting the phosphorylation status of critical myofibrillar and Ca<sup>2+</sup>-handling proteins. Though SB203580 had a limited impact on widespread protein changes in HF, its biosignature revealed preserved mitochondrial energetics and reduced oxidative and inflammatory stress.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-06-01T13:52:36.587Z","creation":"2026-04-08T13:05:35.333Z"},"accession":"S-EPMC12371761","cross_references":{"pubmed":["40860715"],"doi":["10.1021/acsomega.5c03687"]}}