{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:55:09Z","timestamp":1787018109350,"version":"build-2736575974"},"reference-count":85,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,4,15]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Myocardial fibrosis is a pathological hallmark of heart failure post infarction, emphasizing the need for innovative treatment strategies. This research assesses the antifibrotic potential of a sodium alginate (SA) hydrogel loaded with extracellular vesicles (EVs) from bone marrow mesenchymal stem cells and PAP (p38\u03b1 antagonistic peptides), aiming to interfere with fibrosis\u2010inducing pathways in myocardial tissue after infarction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      We induced fibrosis in mouse cardiac fibroblasts through hypoxia and disrupted the\n                      <jats:italic toggle=\"no\">Mapk14<\/jats:italic>\n                      gene to study its contribution to fibrosis. Mesenchymal stem cell\u2010derived EVs, loaded with PAP, were encapsulated in the SA hydrogel (EVs\u2010PAP@SA). The formulation was tested in\u00a0vitro for its effect on fibrotic marker expression and cell behavior, and in\u00a0vivo in a murine model of myocardial infarction for its therapeutic efficacy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">Map k14 silencing showed a decrease in the fibrotic response of cardiac fibroblasts. Treatment with the EVs\u2010PAP@SA hydrogel notably reduced profibrotic signaling, increased cell proliferation and migration, and lowered apoptosis rates. The in\u00a0vivo treatment with the hydrogel post myocardial infarction significantly diminished myocardial fibrosis and improved cardiac performance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">The study endorses the SA hydrogel as an effective vehicle for delivering mesenchymal stem cell\u2010derived EVs and PAP to the heart post myocardial infarction, providing a novel approach for modulating myocardial fibrosis and promoting cardiac healing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.124.036887","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T08:11:30Z","timestamp":1743667890000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Sodium Alginate Hydrogel Infusion of Bone Marrow Mesenchymal Stem Cell\u2010Derived Extracellular Vesicles and p38\u03b1 Antagonistic Peptides in Myocardial Infarction Fibrosis Mitigation"],"prefix":"10.1161","volume":"14","author":[{"given":"Siyao","family":"Chen","sequence":"first","affiliation":[{"name":"Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Zeng","sequence":"additional","affiliation":[{"name":"Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meifeng","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiade","family":"Zhu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3946-0760","authenticated-orcid":false,"given":"Yijin","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University","place":["Guangzhou, 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