{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:45:48Z","timestamp":1782992748352,"version":"3.54.5"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,3,3]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Myocardial infarction (MI) remains a major cause of morbidity and mortality worldwide. MFAP5 (microfibrillar\u2010associated protein 5) is an extracellular\u2010matrix associated secreted glycoprotein whose cardiac function is unknown. This study aimed to explore the origin, expression, function, and potential mechanisms of MFAP5 in MI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">Single\u2010cell analysis and immunohistochemistry were used to determine the origin and expression of MFAP5. Global MFAP5\u2010knockout (KO) mice and adeno\u2010associated virus 9\u2010mediated cardiac fibroblast\u2010specific overexpression mice were used to investigate the function of MFAP5 in\u00a0vivo. RNA sequencing and ingenuity pathway analysis revealed potential mechanisms. Coimmunoprecipitation and confocal microscopy identified molecular interaction domains. rMFAP5 (recombinant MFAP5 protein) and plasmid\u2010mediated intracellular overexpression revealed the effects of MFAP5 on cardiomyocytes under oxygen\u2013glucose deprivation conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">MFAP5 was significantly increased in both human and mouse heart tissues during MI, predominantly derived from activated cardiac fibroblasts. In\u00a0vivo, MFAP5\u2010knockout exacerbated cardiac dysfunction, enlarged infarct size and increased cardiomyocyte apoptosis during the acute phase of MI. Cardiac fibroblast\u2010specific overexpression of MFAP5 exerted a protective effect. In\u00a0vitro, MFAP5 significantly inhibited apoptosis in cardiomyocytes under oxygen\u2013glucose deprivation stimulation. Mechanistically, MFAP5 derived from fibroblasts interacted with the extracellular EGF (epidermal growth factor) repeats of the NOTCH2 receptor on the surface of cardiomyocytes via its MBD domain, promoting shedding of the extracellular fragment of NOTCH2 and generation of the NICD2 (NOTCH2 intracellular domain). MFAP5 inhibited cardiomyocyte apoptosis by activating NOTCH2 signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Fibroblast\u2010derived MFAP5 engages cardiomyocyte NOTCH2 to inhibit apoptosis and exerts cardioprotective effects after MI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.045111","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T11:13:02Z","timestamp":1771931582000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Fibroblast\u2010Derived Microfibrillar\u2010Associated Protein 5 Exerts Cardioprotective Effects After Myocardial Infarction by Activating the NOTCH2 Signaling in Cardiomyocytes"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7191-1196","authenticated-orcid":false,"given":"Jiuqi","family":"Guo","sequence":"first","affiliation":[{"name":"The First Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilin","family":"Gu","sequence":"additional","affiliation":[{"name":"The First Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhi","family":"Lin","sequence":"additional","affiliation":[{"name":"The First Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongqian","family":"Tao","sequence":"additional","affiliation":[{"name":"The First Hospital of China Medical University","place":["Shenyang, 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