{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T12:46:21Z","timestamp":1785847581394,"version":"3.56.0"},"reference-count":40,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangdong Key Clinical Specialty","award":["2024A03J0296"],"award-info":[{"award-number":["2024A03J0296"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>Post-myocardial infarction (MI) remodeling is accompanied by metabolic stress, but the myocardial genes associated with copper handling are poorly defined. We sought to prioritize a tissue-derived candidate rather than establish a copper-dependent mechanism. Regional MI transcriptomes and an in-house left anterior descending coronary artery ligation mouse RNA-sequencing cohort were integrated with protein quantitative trait locus-based Mendelian randomization (MR). Follow-up comprised local and external tissue validation, cardiac single-cell RNA sequencing, Genotype-Tissue Expression co-expression, computational perturbation, and CRIP2 knockdown or overexpression in H9c2 cells exposed to hypoxia\/reoxygenation (H\/R). CRIP2 showed a nominal protective-direction MR association (odds ratio 0.831, 95% confidence interval 0.735\u20130.939; p = 0.0031), but did not pass the Bonferroni threshold. Crip2 was lower in the local MI model (p = 0.0168; n = 5 per group) and in an independent dataset. A prespecified lipoylated-tricarboxylic-acid module was negatively enriched after MI (normalized enrichment score \u22121.63; false discovery rate 0.012), whereas the broader copper-homeostasis set was not significant. Single-cell data localized Crip2 mainly to cardiomyocytes, but were not adequately replicated for condition-level inference. Under H\/R, Atp7a was the only copper-handling transcript whose knockdown-by-oxygen interaction remained significant after adjustment (q = 0.0405). CRIP2 overexpression was associated with higher Cell Counting Kit-8 metabolic activity during H\/R (interaction p = 0.00551), whereas the knockdown interaction was not significant. Copper abundance, mitochondrial function, and cuproptosis markers were not measured. The data prioritize CRIP2 for mechanistic study, but do not show that it regulates copper flux or post-MI remodeling.<\/jats:p>","DOI":"10.3390\/cimb48080767","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T08:52:01Z","timestamp":1785228721000},"page":"767","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Analysis Prioritizes CRIP2 as a Candidate Associated with Myocardial Copper-Handling Responses After Myocardial Infarction"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0033-0512","authenticated-orcid":false,"given":"Zhengqi","family":"Qiu","sequence":"first","affiliation":[{"name":"Department of Applied Psychology, School of Health Management, Guangzhou Medical University, Guangzhou 510182, China"},{"name":"Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou Medical University, Guangzhou 510260, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6131-1623","authenticated-orcid":false,"given":"Xingya","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Applied Psychology, School of Health Management, Guangzhou Medical University, Guangzhou 510182, China"},{"name":"Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou Medical University, Guangzhou 510260, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Applied Psychology, School of Health Management, Guangzhou Medical University, Guangzhou 510182, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2350","DOI":"10.1016\/j.jacc.2023.11.007","article-title":"Global Burden of Cardiovascular Diseases and Risks, 1990\u20132022","volume":"82","author":"Mensah","year":"2023","journal-title":"J. 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