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Early diagnosis remains a challenge due to limited early biomarkers, leading to high morbidity. Here, we have systematically characterized acute (up to 5\u00a0h) CME-induced MINOCA in comparison to MI using clinical markers, histology, multi-ELISAs, miRNA profiling, and proteomics in a translational porcine animal model. CME-induced MINOCA model was created by injecting autologous microthrombi, generated by carotid crush maneuver, into the coronary arteries, whereas MI was induced by LAD balloon occlusion\/reperfusion. MINOCA animals exhibited low troponin (547.0\u2009\u00b1\u2009489.2\u00a0ng\/L) and creatine kinase (1827.8\u2009\u00b1\u2009677.3\u00a0U\/L) levels, as well as infarct size (2.3\u2009\u00b1\u20090.8%), necrosis (7.6\u2009\u00b1\u20093.2%), and interstitial hemorrhage (0.6\u2009\u00b1\u20090.4%). Immune cell infiltration surrounding MINOCA microthrombi sites was significantly higher (1532\u2009\u00b1\u2009722 cells\/mm<jats:sup>2<\/jats:sup>) in comparison to MI infarct zones (470\u2009\u00b1\u2009320 cells\/mm<jats:sup>2<\/jats:sup>). Furthermore, cytokine profiling showed elevated IL-1\u03b1 and IL-1\u03b2 in both groups, higher IL-10 in MINOCA, and higher IFN-y in MI. The MINOCA-specific pro-inflammatory miRNA, ssc-miR-802, was identified. Plasma proteomic analysis revealed leukotriene signaling as a MINOCA inflammatory pathway with augmented leukotriene-A4-hydrolase levels. Its product, leukotriene B4, was increased in MINOCA serum at 150\u00a0min (1031\u2009\u00b1\u2009537.6\u00a0pg\/mL) and 300\u00a0min (1309\u2009\u00b1\u2009640.8\u00a0pg\/mL) and in tissue (408.2\u2009\u00b1\u200992.12\u00a0pg\/mL) vs. MI (428.9\u2009\u00b1\u20099.483\u00a0pg\/mL in serum at 150\u00a0min, 308.76\u2009\u00b1\u20095.484\u00a0pg\/mL in serum at 300\u00a0min, and 76.22\u2009\u00b1\u200931.12\u00a0pg\/mL in tissue). In summary, CME-induced MINOCA elicits a distinct pro-inflammatory leukotriene response compared to MI, presenting a new acute MINOCA diagnostic and therapeutic target.<\/jats:p>","DOI":"10.1007\/s00395-025-01118-9","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T07:49:31Z","timestamp":1749800971000},"page":"657-675","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Molecular screening in a translational large animal trial identifies a differential inflammatory response for MINOCA"],"prefix":"10.1007","volume":"120","author":[{"given":"Jasper","family":"Iske","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua M.","family":"Mesfin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Wolint","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Weisskopf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christien","family":"Beez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henriette","family":"Thau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian T.","family":"Stoeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"January M.","family":"Weiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie M.","family":"Hierweger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"van Gelder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorald","family":"Stolte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuri","family":"\u00dcnesen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross","family":"Straughan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas S. J.","family":"Eckholt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Trimmel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Beule","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Meyborg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo Z.","family":"Nazari-Shafti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volkmar","family":"Falk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian Y.","family":"Emmert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6744-2928","authenticated-orcid":false,"given":"Nikola","family":"Cesarovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,13]]},"reference":[{"key":"1118_CR1","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1007\/s00380-021-01956-2","volume":"37","author":"C Adams","year":"2021","unstructured":"Adams C, Sawhney G, Singh K (2021) Comparing pharmacotherapy in MINOCA versus medically managed obstructive acute coronary syndrome. 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