{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:33Z","timestamp":1787028513296,"version":"build-2736575974"},"reference-count":98,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T00:00:00Z","timestamp":1686787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["JP19H03442"],"award-info":[{"award-number":["JP19H03442"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Japan Heart Foundation Research","award":["JP19H03442"],"award-info":[{"award-number":["JP19H03442"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Adverse ventricular remodeling after myocardial infarction (MI) is progressive ventricular dilatation associated with heart failure for weeks or months and is currently regarded as the most critical sequela of MI. It is explained by inadequate tissue repair due to dysregulated inflammation during the acute stage; however, its pathophysiology remains unclear. Tenascin-C (TNC), an original member of the matricellular protein family, is highly up-regulated in the acute stage after MI, and a high peak in its serum level predicts an increased risk of adverse ventricular remodeling in the chronic stage. Experimental TNC-deficient or -overexpressing mouse models have suggested the diverse functions of TNC, particularly its pro-inflammatory effects on macrophages. The present study investigated the roles of TNC during human myocardial repair. We initially categorized the healing process into four phases: inflammatory, granulation, fibrogenic, and scar phases. We then immunohistochemically examined human autopsy samples at the different stages after MI and performed detailed mapping of TNC in human myocardial repair with a focus on lymphangiogenesis, the role of which has recently been attracting increasing attention as a mechanism to resolve inflammation. The direct effects of TNC on human lymphatic endothelial cells were also assessed by RNA sequencing. The results obtained support the potential roles of TNC in the regulation of macrophages, sprouting angiogenesis, the recruitment of myofibroblasts, and the early formation of collagen fibrils during the inflammatory phase to the early granulation phase of human MI. Lymphangiogenesis was observed after the expression of TNC was down-regulated. In vitro results revealed that TNC modestly down-regulated genes related to nuclear division, cell division, and cell migration in lymphatic endothelial cells, suggesting its inhibitory effects on lymphatic endothelial cells. The present results indicate that TNC induces prolonged over-inflammation by suppressing lymphangiogenesis, which may be one of the mechanisms underlying adverse post-infarct remodeling.<\/jats:p>","DOI":"10.3390\/ijms241210184","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T01:31:31Z","timestamp":1686879091000},"page":"10184","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Tenascin-C in Tissue Repair after Myocardial Infarction in Humans"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4357-590X","authenticated-orcid":false,"given":"Kenta","family":"Matsui","sequence":"first","affiliation":[{"name":"Department of Pathology and Matrix Biology, Graduate School of Medicine, Mie University, 2-174 Edobashi, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sota","family":"Torii","sequence":"additional","affiliation":[{"name":"Department of Pathology and Matrix Biology, Graduate School of Medicine, Mie University, 2-174 Edobashi, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Pathology and Matrix Biology, Graduate School of Medicine, Mie University, 2-174 Edobashi, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3935-328X","authenticated-orcid":false,"given":"Kazuaki","family":"Maruyama","sequence":"additional","affiliation":[{"name":"Department of Pathology and Matrix Biology, Graduate School of Medicine, Mie University, 2-174 Edobashi, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomio","family":"Arai","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, 3-52 Sakaecho, Itabashi-ku, Tokyo 173-0015, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoko","family":"Imanaka-Yoshida","sequence":"additional","affiliation":[{"name":"Department of Pathology and Matrix Biology, Graduate School of Medicine, Mie University, 2-174 Edobashi, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0140-6736(16)30677-8","article-title":"Acute myocardial infarction","volume":"389","author":"Reed","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e027600","DOI":"10.1161\/JAHA.122.027600","article-title":"Impact of Reperfusion on Temporal Immune Cell Dynamics After Myocardial Infarction","volume":"12","author":"Zhang","year":"2023","journal-title":"J. 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