Dynamic changes and effects of itaconate in myocardial ischemia-reperfusion injury

Shan Wenju; Cui Jun; Jian Yuhong; Feng Linqi; Yi Wei; Sun Yang

doi:10.13498/j.cnki.chin.j.ecc.2024.02.13

Abstract：Objective To explore the dynamics changes and effects of itaconate in myocardial ischemia-reperfusion injury(MIRI)in mice.Methods The MIRI model was constructed to detect changes in the content of itaconate in cardiac tissues and plasma.Comparison of changes in cardiac function after MIRI in mice with exogenous itaconate by intraperitoneal injection were conducted.The cell viability was assessed by the cell counting reagent(CCK-8),and cell damage was evaluated by the detection of lactate dehydrogenase(LDH)content in the hypoxia/reoxygenation(H/R)model for H9C2 cells in vitro.Results Compared with the sham surgery(Sham)group,the expression of itaconate in cardiac tissues after I/R showed an increasing trend and was more significantly elevated at 24h than that at 6h(P<0.001)whereas the plasma expression was significantly elevated at 6h(P<0.0001)and then showed a decreasing trend,and was significantly lower at 24h after I/R(P<0.05),but still significantly higher than that in the Sham group(P<0.01).Itaconate-treated significantly attenuated cardiac dysfunction after MIRI in C57BL/6 mice compared with the H/R group alone,itaconate significantly increased cell viability and improved hypoxia/reoxygenation-induced injury.Conclusion Itaconate is consistently elevated in cardiac tissue after I/R,whereas it increases and then decreases in plasma.Exogenous itaconate can improve the cardiac dysfunction after MIRI in mice and protect against hypoxia/reoxygenation injury in H9C2 cells.