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Insulin\u2010like growth factor\u2010II receptor \u03b1 (IGF\u2010IIR\u03b1) acts as a stress\u2010inducible negative regulator. This study focused on the substantial impact of heightened expression of IGF\u2010IIR\u03b1 in cardiac myoblasts and its association with the exacerbation of cardiac dysfunction. Using lipopolysaccharide (LPS)\u2010induced H9c2 cardiac myoblasts as a model for sepsis, we aimed to elucidate the molecular interactions between IGF\u2010IIR\u03b1 and LPS in exacerbating cardiac injury. Our findings demonstrated a synergistic induction of cardiac inflammation and hypertrophy by LPS stimulation and IGF\u2010IIR\u03b1 overexpression, leading to decreased cell survival. Excessive calcineurin activity, triggered by this combined condition, was identified as a key factor exacerbating the negative effects on cell survival. Cellular changes such as cell enlargement, disrupted actin filaments, and upregulation of hypertrophy\u2010related and inflammation\u2010related proteins contributed to the overall hypertrophic and inflammatory responses. Overexpression of IGF\u2010IIR\u03b1 also exacerbated apoptosis induced by LPS in H9c2 cardiac myoblasts. Inhibiting calcineurin in LPS\u2010treated H9c2 cardiac myoblasts with IGF\u2010IIR\u03b1 overexpression effectively reversed the detrimental effects, reducing cell damage and mitigating apoptosis\u2010related cardiac mechanisms. Our study suggests that under sepsis\u2010like conditions in the heart with IGF\u2010IIR\u03b1 overexpression, hyperactivation of calcineurin worsens cardiac damage. Suppressing IGF\u2010IIR\u03b1 and calcineurin expression could be a potential intervention to alleviate the impact of the illness and improve cardiac function.<\/jats:p>","DOI":"10.1002\/tox.24385","type":"journal-article","created":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T07:55:30Z","timestamp":1723017330000},"page":"5173-5186","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Enhanced\n                    <scp>IGF<\/scp>\n                    \u2010\n                    <scp>IIR\u03b1<\/scp>\n                    Expression Exacerbates Lipopolysaccharide\u2010Induced Cardiac Inflammation, Hypertrophy, and Apoptosis Through Calcineurin Activation"],"prefix":"10.1002","volume":"39","author":[{"given":"Khwanchit","family":"Boonha","sequence":"first","affiliation":[{"name":"Graduate Institute of Biomedical Sciences China Medical University  Taichung Taiwan"},{"name":"Cardiovascular and Mitochondrial Related 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