线粒体通透性转换孔
半乳糖凝集素-3
缺血
再灌注损伤
半乳糖凝集素
细胞凋亡
免疫染色
标记法
药理学
体内
化学
生物
医学
程序性细胞死亡
内科学
免疫组织化学
生物化学
生物技术
作者
Dan Mo,Wen Tian,Huinan Zhang,Ying-Da Feng,Yang Sun,Wei Quan,Xiao-Wei Hao,Xueying Wang,Xiao-Xiao Liu,Chen Li,Wei Cao,Wenjuan Liu,Xiaoqiang Li
标识
DOI:10.1016/j.ejphar.2019.172701
摘要
Myocardial ischemia/reperfusion (IR) injury is caused by the restoration of the coronary blood flow following an ischemic episode. Accumulating evidence suggests that galectin-3, a β-galactoside-binding lectin, acts as a biomarker in heart disease. However, it remains unclear whether manipulating galectin-3 affects the susceptibility of the heart to IR injury. In this study, RNA sequencing (RNA-seq) analysis identified that Lgals3 (galecin-3) plays an indispensable role in IR-induced cardiac damage. Immunostaining and immunoblot assays confirmed that the expression of galectin-3 was markedly increased in myocardial IR injury both in vivo and in vitro. Echocardiographic analysis showed that cardiac dysfunction in experimental IR injury was significantly attenuated by galectin-3 inhibitors including pectin (1%, i.p.) from citrus and binding peptide G3-C12 (5.0 mg/kg, i.p.). Galectin-3 inhibitor-treated mice exhibited smaller infarct sizes and decreased tissue injury. Furthermore, TUNEL staining showed that galectin-3 inhibition suppressed IR-mediated cardiomyocyte apoptosis. Mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (mPTP) levels were well-preserved and IR-induced changes of mitochondrial cyto c, cytosol cyto c, caspase-9, caspase-3, Bcl-2 and Bax in the galectin-3 inhibitor-treated groups were observed. Our findings indicate that the pathological upregulation of galectin-3 contributes to IR-induced cardiac dysfunction and that galectin-3 inhibition ameliorates myocardial injury, highlighting its therapeutic potential.
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