{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:20:10Z","timestamp":1790713210651,"version":"4.1.0"},"reference-count":77,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["2R01HL140411-05A1"],"award-info":[{"award-number":["2R01HL140411-05A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Florida Department of Health DeSantis","award":["91803004"],"award-info":[{"award-number":["91803004"]}]},{"name":"MUG22 DeSantis","award":["91925093"],"award-info":[{"award-number":["91925093"]}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["R01-GM063904"],"award-info":[{"award-number":["R01-GM063904"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Myocardial infarction (MI) remains a leading cause of mortality worldwide, yet effective cardioprotective strategies remain limited in clinical settings. Vascular endothelial growth factor B (VEGFB) has emerged as a promising therapeutic candidate in MI, but the role of its co-receptor, Neuropilin-1 (NRP1), in cardiomyocyte (CM) survival under ischemic stress remains poorly understood. Here, we investigated VEGFB-NRP1 signaling using an in vivo zebrafish model of cardiac injury as well as in vitro hypoxia models in CMs. We demonstrated that VEGFB overexpression conferred protection against ischemic injury and enhanced cardiac regeneration in the zebrafish heart. Mechanistically, we showed that VEGFB treatment enhances CM viability through reducing reactive oxygen species (ROS), ferroptosis activation, and preserving mitochondrial integrity. We also demonstrated that NRP1 knockdown in the CMs abolished the VEGFB-mediated protective effects, indicating the significant role of NRP1 signaling in VEGFB-induced cardioprotective effects in MI. Lastly, using transcriptome analysis, we confirmed that VEGFB induces anti-apoptotic and anti-ferroptosis gene programs in CMs in response to hypoxic stress. Collectively, our findings provide mechanistic insight into cell death activation pathways, including ferroptosis, in response to ischemic stress and further validate the therapeutic potential of VEGFB in promoting CM survival in ischemic heart disease.<\/jats:p>","DOI":"10.3390\/cells14201642","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T15:36:31Z","timestamp":1761060991000},"page":"1642","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Vascular Endothelial Growth Factor B Modulates Cardiac Functions via Ferroptosis Pathways in Post-Myocardial Infarction"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4259-5604","authenticated-orcid":false,"given":"Sai Manasa","family":"Varanasi","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Sciences, Jacksonville, FL 32224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankit","family":"Sabharwal","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA"},{"name":"Department of Pediatrics, Dell Pediatric Research Institute, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Center for Rare Disease, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9896-0746","authenticated-orcid":false,"given":"Shreyartha","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL 32224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huzaifa","family":"Muhammad","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Sciences, Jacksonville, FL 32224, USA"},{"name":"College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riya","family":"Kar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Sciences, Jacksonville, FL 32224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carter","family":"Magnano","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Sciences, Jacksonville, FL 32224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anya","family":"Dorairaj","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Sciences, Jacksonville, FL 32224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enfeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Sciences, Jacksonville, FL 32224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamit","family":"Dutta","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Sciences, Jacksonville, FL 32224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pritam","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Sciences, Jacksonville, FL 32224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C.","family":"Ekker","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA"},{"name":"Department of Pediatrics, Dell Pediatric Research Institute, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Center for Rare Disease, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Sciences, Jacksonville, FL 32224, USA"},{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA"},{"name":"Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1858-5054","authenticated-orcid":false,"given":"Debabrata","family":"Mukhopadhyay","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Sciences, Jacksonville, FL 32224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5894-1108","authenticated-orcid":false,"given":"Ramcharan Singh","family":"Angom","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Sciences, Jacksonville, FL 32224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.amjmed.2016.05.018","article-title":"Mental Health and Cardiovascular Disease","volume":"129","author":"Chaddha","year":"2016","journal-title":"Am. 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