1. Cardioprotective effects of galectin-3 inhibition against ischemia/reperfusion injury.
- Author
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Mo, Dan, Tian, Wen, Zhang, Hui-Nan, Feng, Ying-Da, Sun, Yang, Quan, Wei, Hao, Xiao-Wei, Wang, Xue-Ying, Liu, Xiao-Xiao, Li, Chen, Cao, Wei, Liu, Wen-Juan, and Li, Xiao-Qiang
- Subjects
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GALECTINS , *MYOCARDIAL reperfusion , *REPERFUSION injury , *CORONARY circulation , *MITOCHONDRIAL membranes , *MEMBRANE potential - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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