{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T06:19:00Z","timestamp":1779344340819,"version":"3.51.4"},"reference-count":28,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T00:00:00Z","timestamp":1710460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lin Huddleston Heart Foundation Fellowship","award":["FLF102056"],"award-info":[{"award-number":["FLF102056"]}]},{"name":"Lin Huddleston Heart Foundation Fellowship","award":["CDF1161506"],"award-info":[{"award-number":["CDF1161506"]}]},{"DOI":"10.13039\/501100001030","name":"National Heart Foundation of Australia","doi-asserted-by":"publisher","award":["FLF102056"],"award-info":[{"award-number":["FLF102056"]}],"id":[{"id":"10.13039\/501100001030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001030","name":"National Heart Foundation of Australia","doi-asserted-by":"publisher","award":["CDF1161506"],"award-info":[{"award-number":["CDF1161506"]}],"id":[{"id":"10.13039\/501100001030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council of Australia","doi-asserted-by":"publisher","award":["FLF102056"],"award-info":[{"award-number":["FLF102056"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council of Australia","doi-asserted-by":"publisher","award":["CDF1161506"],"award-info":[{"award-number":["CDF1161506"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Angiogenesis is a critical physiological response to ischemia but becomes pathological when dysregulated and driven excessively by inflammation. We recently identified a novel angiogenic role for tripartite-motif-containing protein 2 (TRIM2) whereby lentiviral shRNA-mediated TRIM2 knockdown impaired endothelial angiogenic functions in vitro. This study sought to determine whether these effects could be translated in vivo and to determine the molecular mechanisms involved. CRISPR\/Cas9-generated Trim2\u2212\/\u2212 mice that underwent a periarterial collar model of inflammation-induced angiogenesis exhibited significantly less adventitial macrophage infiltration relative to wildtype (WT) littermates, concomitant with decreased mRNA expression of macrophage marker Cd68 and reduced adventitial proliferating neovessels. Mechanistically, TRIM2 knockdown in endothelial cells in vitro attenuated inflammation-driven induction of critical angiogenic mediators, including nuclear HIF-1\u03b1, and curbed the phosphorylation of downstream effector eNOS. Conversely, in a hindlimb ischemia model of hypoxia-mediated angiogenesis, there were no differences in blood flow reperfusion to the ischemic hindlimbs of Trim2\u2212\/\u2212 and WT mice despite a decrease in proliferating neovessels and arterioles. TRIM2 knockdown in vitro attenuated hypoxia-driven induction of nuclear HIF-1\u03b1 but had no further downstream effects on other angiogenic proteins. Our study has implications for understanding the role of TRIM2 in the regulation of angiogenesis in both pathophysiological contexts.<\/jats:p>","DOI":"10.3390\/ijms25063343","type":"journal-article","created":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T12:02:39Z","timestamp":1710504159000},"page":"3343","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["TRIM2 Selectively Regulates Inflammation-Driven Pathological Angiogenesis without Affecting Physiological Hypoxia-Mediated Angiogenesis"],"prefix":"10.3390","volume":"25","author":[{"given":"Nathan K. P.","family":"Wong","sequence":"first","affiliation":[{"name":"Vascular Research Centre, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia"},{"name":"Faculty of Medicine and Health, The University of Sydney School of Medicine, Camperdown, NSW 2050, Australia"},{"name":"Department of Cardiology, St. Vincent\u2019s Hospital, Darlinghurst, NSW 2010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9992-1181","authenticated-orcid":false,"given":"Emma L.","family":"Solly","sequence":"additional","affiliation":[{"name":"Vascular Research Centre, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia"},{"name":"Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5005, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4265-0996","authenticated-orcid":false,"given":"Richard","family":"Le","sequence":"additional","affiliation":[{"name":"Vascular Research Centre, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia"},{"name":"College of Medicine and Public Health, Flinders University, Adelaide, SA 5042, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria A.","family":"Nankivell","sequence":"additional","affiliation":[{"name":"Vascular Research Centre, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia"},{"name":"Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5005, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jocelyne","family":"Mulangala","sequence":"additional","affiliation":[{"name":"Vascular Research Centre, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia"},{"name":"Heart Foundation, Brisbane, QLD 4000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J.","family":"Psaltis","sequence":"additional","affiliation":[{"name":"Vascular Research Centre, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia"},{"name":"Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5005, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen J.","family":"Nicholls","sequence":"additional","affiliation":[{"name":"Victorian Heart Institute, Monash University, Clayton, VIC 3800, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin K. C.","family":"Ng","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health, The University of Sydney School of Medicine, Camperdown, NSW 2050, Australia"},{"name":"Department of Cardiology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0682-8760","authenticated-orcid":false,"given":"Christina A.","family":"Bursill","sequence":"additional","affiliation":[{"name":"Vascular Research Centre, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia"},{"name":"Faculty of Medicine and Health, The University of Sydney School of Medicine, Camperdown, NSW 2050, Australia"},{"name":"Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5005, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1875-4882","authenticated-orcid":false,"given":"Joanne T. M.","family":"Tan","sequence":"additional","affiliation":[{"name":"Vascular Research Centre, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia"},{"name":"Faculty of Medicine and Health, The University of Sydney School of Medicine, Camperdown, NSW 2050, Australia"},{"name":"Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5005, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1161\/ATVBAHA.108.181644","article-title":"Vascular responses to hypoxia and ischemia","volume":"30","author":"Semenza","year":"2010","journal-title":"Arterioscler. Thromb. Vasc. 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