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This risk locus encodes a long noncoding RNA, ANRIL, which has been suggested to regulate the neighboring cyclin\u2010dependent kinase inhibitors 2A and B (<jats:italic>Cdkn2A\/B<\/jats:italic>), the key regulators of cell proliferation. In this study, we aimed to clarify the role of the 9p21.3 risk locus in acute and chronic myocardial ischemia in mice. Mice carrying a deletion equivalent to the human CAD risk interval (Chr4<jats:sup>\u039470kb\/\u039470kb<\/jats:sup>) and wild type mice were exposed to MI and followed until 5\u2009days or 4\u2009weeks. In the wild type mice, expression of a lncRNA, Ak148321, was increased after MI, and Cdkn2a was upregulated in chronic ischemia. Chr4<jats:sup>\u039470kb\/\u039470kb<\/jats:sup> downregulated both <jats:italic>Cdkn2a\/b<\/jats:italic>, but this did not affect the survival or cardiac pathology after MI. These results suggest that the 9p21.3 locus is activated in response to cardiac ischemia. However, deficiency in the risk locus does not play a role in the cardiac pathophysiology in mice, supporting the studies suggesting the risk locus being more involved in the development of CAD, rather than the subsequent MI.<\/jats:p>","DOI":"10.14814\/phy2.70344","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T02:26:10Z","timestamp":1747967170000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Myocardial infarction activates the 9p21.3 orthologous locus expression, but its absence does not alter cardiac pathophysiology in ischemia"],"prefix":"10.14814","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6096-2402","authenticated-orcid":false,"given":"Sanna","family":"Kettunen","sequence":"first","affiliation":[{"name":"A.I. 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