{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T07:05:29Z","timestamp":1789974329993,"version":"4.0.1"},"reference-count":47,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473922"],"award-info":[{"award-number":["82473922"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>\n                      Myocardial infarction (MI) triggers extracellular matrix (ECM) remodelling and oxidative stress, leading to cardiomyocyte injury and adverse cardiac remodelling.\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.guidetopharmacology.org\/GRAC\/LigandDisplayForward?ligandId=6804\">Heparan sulphate (HS)<\/jats:ext-link>\n                      , a major ECM component, plays an important role in regulating cell\u2013cell communication and stress responses. Exostosin\u20101 (EXT1), a glycosyltransferase essential for HS biosynthesis, is highly expressed in cardiomyocytes, yet its role in post\u2010MI repair remains incompletely understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      We investigated the role of cardiomyocyte EXT1 in myocardial ischaemic injury using genetic and pharmacological approaches\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Cardiomyocyte\u2010specific\n                      <jats:italic>Ext1<\/jats:italic>\n                      silencing exacerbated infarct size, mitochondrial abnormalities, oxidative stress and fibrosis following permanent left anterior descending coronary artery ligation, whereas EXT1 preserved mitochondrial integrity and redox balance under hypoxic stress. Mechanistically, infiltrating macrophages released superoxide dismutase 2 (SOD2), and myocardial accumulation of macrophage\u2010derived SOD2 was reduced after EXT1 depletion or HS disruption. HS disruption impaired SOD2 accumulation and worsened ischaemic injury, while pharmacological activation of macrophages with dimethyl itaconate (DMI) enhanced SOD2 release and conferred cardioprotection in an EXT1\u2010dependent manner.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>These findings identify cardiomyocyte EXT1 as a regulator of HS\u2010dependent macrophage\u2013cardiomyocyte crosstalk that limits oxidative damage and adverse remodelling after MI. They further suggest that modulation of the EXT1\u2013HS axis, including pharmacological enhancement of macrophage antioxidant signalling by DMI, may represent a strategy to reinforce endogenous cardioprotection after ischaemic injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70663","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T06:51:18Z","timestamp":1789973478000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["EXT1 in cardiomyocytes promotes heparan sulphate\u2010dependent accumulation of macrophage\u2010derived SOD2 to protect against post\u2010myocardial infarction injury"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4336-3625","authenticated-orcid":false,"given":"Xie","family":"Li","sequence":"first","affiliation":[{"name":"School of Life Science and Technology China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7618-7154","authenticated-orcid":false,"given":"Yinan","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9269-8576","authenticated-orcid":false,"given":"Xiaozhi","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2182-3249","authenticated-orcid":false,"given":"Yating","family":"Li","sequence":"additional","affiliation":[{"name":"School of Science China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2961-2924","authenticated-orcid":false,"given":"Jie","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Science China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7823-1222","authenticated-orcid":false,"given":"Mengjie","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2768-274X","authenticated-orcid":false,"given":"Shilin","family":"Jia","sequence":"additional","affiliation":[{"name":"School of Science China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9997-6816","authenticated-orcid":false,"given":"Yuru","family":"Shao","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8399-6867","authenticated-orcid":false,"given":"Marta","family":"Llovera","sequence":"additional","affiliation":[{"name":"Universitat de Lleida  Lleida Spain"},{"name":"Institut de Recerca Biomedica de Lleida (IRBLLEIDA)  Lleida Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3347-5021","authenticated-orcid":false,"given":"Fangrong","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Science China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5638-9914","authenticated-orcid":false,"given":"Ruiyan","family":"Li","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5953-3874","authenticated-orcid":false,"given":"Yuhang","family":"Sheng","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4995-3553","authenticated-orcid":false,"given":"Liang","family":"Jin","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0047-8533","authenticated-orcid":false,"given":"Daniel","family":"Sanchis","sequence":"additional","affiliation":[{"name":"Universitat de Lleida  Lleida Spain"},{"name":"Institut de Recerca Biomedica de Lleida (IRBLLEIDA)  Lleida Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1162-0216","authenticated-orcid":false,"given":"Junmei","family":"Ye","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70234"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70229"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/adtp.202100036"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0276-y"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/hc0802.104502"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05817"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.11.008"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.22.010605.093433"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703560200"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2013.10.001"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.09.033"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.08.002"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.17441"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00022.2018"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci13737"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.71.110601.135458"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.121.055888"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.89.5.1982"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c150006"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci87491"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvac113"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2047343"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2013.5695"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.06.022"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-018-0712-z"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32284-2"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht529"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.9798"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s000110300037"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.110.235689"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm14020653"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25986"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.05.035"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a004952"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-019-0725-2"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0805862105"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03818-3"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.07.067"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.106.644609"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.89377"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2026.104228"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2012.07.013"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.113.007497"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0136518"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-019-0260-8"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70663","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.70663","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70663","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T06:51:20Z","timestamp":1789973480000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.70663"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,20]]},"references-count":47,"alternative-id":["10.1111\/bph.70663"],"URL":"https:\/\/doi.org\/10.1111\/bph.70663","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,20]]},"assertion":[{"value":"2026-05-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"bph.70663"}}