Pathological upregulation of galectin-3 contributes to ischemia/reperfusion-induced cardiac dysfunction

OBJECTIVE Myocardial ischemia/reperfusion(I/R) injury is caused by the restoration of the coronary blood flow following an ischemic episode. Accumulating evidence suggests that galectin-3, a β-galactosidebinding lectin, acts as a biomarker in heart disease. The aim of this study is to explore whether galectin-3 affects the susceptibility of the heart to I/R injury. METHODS Male C57 BL/6 J mice were subjected to myocardial30 min/24 h ischemia/reperfusion. Then, RNA sequencing(RNA-seq) was performed to identify the differentially expressed genes in the I/R group compared with the sham group. Echocardiography, H&E and TTC staining,TUNEL, a 12 h/1 h hypoxia/reoxygenation(H/R), mitochondrial membrane potential(MMP), Western blotting and pharmacological intervention were conducted to evaluate pathological damage or to elucidate the mechanisms of galectin-3 affects the susceptibility of the heart to I/R injury in vivo and in vitro. RESULTS 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 I/R injury both in vivo and in vitro. Echocardiographic analysis showed that cardiac dysfunction in experimental I/R injury was significantly attenuated by galectin-3 inhibitors including pectin(1%, ip) from citrus and binding peptide G3-C12(5.0 mg·kg-1, ip). Galectin-3 inhibitor-treated mice exhibited smaller infarct sizes and decreased tissue injury. Furthermore, TUNEL staining showed that galectin-3 inhibition suppressed I/R-mediated cardiomyocyte apoptosis.MMP and mitochondrial permeability transition pore(m PTP) levels were well-preserved and I/R-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. CONCLUSION Our findings indicate that the pathological upregulation of galectin-3 contributes to I/R-induced cardiac dysfunction and that galectin-3 inhibition ameliorates myocardial injury, highlighting its therapeutic potential.