{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:14:13Z","timestamp":1760148853218,"version":"build-2065373602"},"reference-count":63,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Roswell Park Cancer Institute, National Cancer Institute","award":["P30CA016056","S10OD010393","S10OD016450","R01HL150266","R21HL154028","K08HL131987","R01HL152090"],"award-info":[{"award-number":["P30CA016056","S10OD010393","S10OD016450","R01HL150266","R21HL154028","K08HL131987","R01HL152090"]}]},{"name":"National Institute of Health (NIH)","award":["P30CA016056","S10OD010393","S10OD016450","R01HL150266","R21HL154028","K08HL131987","R01HL152090"],"award-info":[{"award-number":["P30CA016056","S10OD010393","S10OD016450","R01HL150266","R21HL154028","K08HL131987","R01HL152090"]}]},{"DOI":"10.13039\/100000002","name":"NIH\/NHLBI","doi-asserted-by":"publisher","award":["P30CA016056","S10OD010393","S10OD016450","R01HL150266","R21HL154028","K08HL131987","R01HL152090"],"award-info":[{"award-number":["P30CA016056","S10OD010393","S10OD016450","R01HL150266","R21HL154028","K08HL131987","R01HL152090"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Cardioprotective effects of N-acetyl-ser-asp-lys-pro (Ac-SDKP) have been reported in preclinical models of myocardial remodeling. However, the rapid degradation of this endogenous peptide in vivo limits its clinical use. Method: To prolong its bioavailability, Ac-SDKP was encapsulated by phosphocholine lipid bilayers (liposomes) similar to mammalian cell membranes. The physical properties of the liposome structures were assessed by dynamic light scattering and scanning electron microscopy. The uptake of Ac-SDKP by RAW 264.7 macrophages and human and murine primary cardiac fibroblasts was confirmed by fluorescence microscopy and flow cytometry. Spectrum computerized tomography and competitive enzyme-linked immunoassays were performed to measure the ex vivo cardiac biodistribution of Ac-SDKP. The biological effects of this novel synthetic compound were examined in cultured macrophages and cardiac fibroblasts and in a murine model of acute myocardial infarction induced by permanent coronary artery ligation. Results: A liposome formulation resulted in the greater uptake of Ac-SDKP than the naked peptide by cultured RAW 264.7 macrophages and cardiac fibroblasts. Liposome-delivered Ac-SDKP decreased fibroinflammatory genes in cultured cardiac fibroblasts co-treated with TGF-\u03b21 and macrophages stimulated with LPS. Serial tissue and serum immunoassays showed the high bioavailability of Ac-SDKP in mouse myocardium and in circulation. Liposome-delivered Ac-SDKP improved cardiac function and reduced myocardial fibroinflammatory responses in mice with acute myocardial infarction. Conclusion: Encapsulation of Ac-SDKP in a cell membrane-like phospholipid bilayer enhances its plasma and tissue bioavailability and offers cardioprotection against ischemic myocardial injury. Future clinical trials can use this novel approach to test small protective endogenous peptides in myocardial remodeling.<\/jats:p>","DOI":"10.3390\/cells12121589","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T01:32:34Z","timestamp":1686274354000},"page":"1589","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Phospholipid Encapsulation of an Anti-Fibrotic Endopeptide to Enhance Cellular Uptake and Myocardial Retention"],"prefix":"10.3390","volume":"12","author":[{"given":"Swati D.","family":"Sonkawade","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Cardiology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14260, USA"},{"name":"Laboratory Medicine, Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shirley","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14260, USA"},{"name":"Laboratory Medicine, Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minhyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarmila","family":"Nepali","sequence":"additional","affiliation":[{"name":"Laboratory Medicine, Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoire-Grace","family":"Karambizi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14260, USA"},{"name":"Laboratory Medicine, Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Sexton","sequence":"additional","affiliation":[{"name":"Laboratory Animal Shared Resource, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven G.","family":"Turowski","sequence":"additional","affiliation":[{"name":"Translational Imaging Shared Resources, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunpeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Case Western Reserve School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5049-4737","authenticated-orcid":false,"given":"Joseph A.","family":"Spernyak","sequence":"additional","affiliation":[{"name":"Translational Imaging Shared Resources, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9052-884X","authenticated-orcid":false,"given":"Jonathan F.","family":"Lovell","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14260, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"George","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sujit","family":"Suwal","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Buffalo State University, Buffalo, NY 14222, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0476-2523","authenticated-orcid":false,"given":"Umesh C.","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14260, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saraswati","family":"Pokharel","sequence":"additional","affiliation":[{"name":"Laboratory Medicine, Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1038\/s41591-021-01457-9","article-title":"A novel treatment for heart failure targets myocardial fibrosis","volume":"27","author":"Cleland","year":"2021","journal-title":"Nat. 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