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Receptor\u2010interacting protein kinase 3\u2010 (RIPK3\u2010) mediated necroptosis has been reported to contribute to cardiac dysfunction. However, the potential protective role of inhibition of RIPK3, a regulator of CaMKII, on cardiac hypertrophy remains unclear. The present study is aimed at investigating how the RIPK3 inhibitor GSK\u2019872 regulates CaMKII activity and exploring its effect on hypertrophic cardiomyopathy (HCM). Wild\u2010type (WT) and RIPK3 gene knockout (RIPK3<jats:sup>-\/-<\/jats:sup>) mice were implanted subcutaneously with Alzet miniosmotic pumps (200\u2009<jats:italic>\u03bc<\/jats:italic>L) and perfused with angiotensin II (AMP\u2010AngII) to induce cardiac hypertrophy. After WT mice were induced by AngII for 72 hours, they were injected with GSK\u2019872 with an intraperitoneal (IP) dose of 6\u2009mg\/kg once a day for two weeks. After this, they were physiologically examined for Echocardiography, myocardial injury, CaMKII activity, necroptosis, RIPK3 expression, mixed lineage kinase domain\u2010like protein (MLKL) phosphorylation, and mitochondrial ultrastructure. The results indicated that deletion of the RIPK3 gene or administration of GSK\u2019872 could reduce CaMKII activity, alleviate oxidative stress, reduce necroptosis, and reverse myocardial injury and cardiac dysfunction caused by AngII\u2010induced cardiac hypertrophy in mice. The present study demonstrated that CaMKII activation and necroptosis augment cardiac hypertrophy in a RIPK3\u2010dependent manner, which may provide therapeutic strategies for HCM. RIPK3 inhibitor GSK\u2019872 has a protective effect on cardiac hypertrophy and could be an efficacious targeted medicine for HCM in clinical treatment.<\/jats:p>","DOI":"10.1155\/2022\/7941374","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T20:50:07Z","timestamp":1659041407000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Ca<sup>2+<\/sup>\/Calmodulin\u2010Dependent Protein Kinase II Regulation by Inhibitor of RIPK3 Protects against Cardiac 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