PKM2 regulated by liquiritin improves ischemia and reperfusion induced endothelial injury and promotes angiogenesis through STAT3 pathway

Alleviating ischemia/reperfusion (I/R) induced cardiac vascular endothelial dysfunction may effectively prevent myocardial I/R injury. Studies showed that PKM2 are associated with a reduction in cardiomyocyte apoptosis and ischemic insult. Liquiritin (LIQ) has attracted attention for its cardioprotective effects. However, whether LIQ can reduce endothelial injury induced by I/R has not been fully explored and the mechanism of PKM2 in this process remains to be elucidated. In our study, we identified that LIQ preconditioning significantly improved cardiac dysfunction and increased angiogenesis after I/R injury, but inhibition of PKM2 markedly deteriorated cardiac function and angiogenesis in vivo. In vitro, experiments have revealed that LIQ significantly promoted angiogenesis, inhibited oxidative stress, apoptosis and inflammation, and then effectively prevented H ₂ O ₂ -induced umbilical vein endothelial cell (HUVECs) damage. LIQ up-regulated PKM2 expression, promoted PKM2 phosphorylation, increased the ratio of p-PKM2 to PKM2, and significantly increased the expression of p-STAT3. However, suppression of PKM2 by shikonin significantly abolished these protective effects. Additionally, it is worth noting that a significant decline in the beneficial effect of LIQ was observed in models that inhibit STAT3. In conclusion, LIQ upregulates PKM2, promotes PKM2 phosphorylation, increases the ratio of p-PKM2 to PKM2, and activates STAT3 pathway to effectively alleviate ECs dysfunction and stimulate angiogenesis, which may be a potential treatment for myocardial I/R injury.