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Here, we aimed to identify protectomiRs in a translational porcine model of acute myocardial infarction (AMI) and to validate their cardiocytoprotective effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>ProtectomiR candidates were selected after systematic analysis of miRNA expression changes in cardiac tissue samples from a closed\u2010chest AMI model in pigs subjected to sham operation, AMI and ischaemic preconditioning, postconditioning or remote preconditioning, respectively. Cross\u2010species orthologue protectomiR candidates were validated in simulated ischaemia\u2013reperfusion injury (sI\/R) model of isolated rat ocardiomyocytes and in human AC16 cells as well. For miR\u2010450a, we performed target prediction and analysed the potential mechanisms of action by GO enrichment and KEGG pathway analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Out of the 220 detected miRNAs, four were up\u2010regulated and 10 were down\u2010regulated due to all three conditionings versus AMI. MiR\u2010450a and miR\u2010451 mimics at 25\u2009nM were protective in rat cardiomyocytes, and miR\u2010450a showed protection in human cardiomyocytes as well. MiR\u2010450a has 3987 predicted mRNA targets in pigs, 4279 in rats and 8328 in humans. Of these, 607 genes are expressed in all three species. A total of 421 common enriched GO terms were identified in all three species, whereas KEGG pathway analysis revealed 13 common pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>This is the first demonstration that miR\u2010450a is associated with cardioprotection by ischaemic conditioning in a clinically relevant porcine model and shows cardiocytoprotective effect in human cardiomyocytes, making it a promising drug candidate. The mechanism of action of miR\u2010450a involves multiple cardioprotective pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>LINKED ARTICLES<\/jats:title><jats:p>This article is part of a themed issue Non\u2010coding RNA Therapeutics. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v182.2\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v182.2\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.17313","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T03:24:16Z","timestamp":1726716256000},"page":"396-416","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Cardioprotective microRNAs (protectomiRs) in a pig model of acute myocardial infarction and cardioprotection by ischaemic conditioning: MiR\u2010450a"],"prefix":"10.1111","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3253-5398","authenticated-orcid":false,"given":"Regina N.","family":"Nagy","sequence":"first","affiliation":[{"name":"Cardiometabolic and HUN\u2010REN\u2010SU System 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