Human Urinary Kallidinogenase (HUK) Alleviates Myocardial Injury in Rats with Coronary Microembolism Through PI3K/Akt/FoxO1 Signaling Pathway.

Abstract

PurposeCoronary artery microembolization (CME) is a severe clinical complication that can cause myocardial infarction, induce myocardial inflammation and apoptosis, ultimately lead to cardiac dysfunction. Human Urinary Kallidinogenase (HUK), a glycoprotein found in human urine, its role and underlying mechanism in CME are still unclear. Therefore, our goal is to explore the effect of HUK on the PI3K/Akt/FoxO1 axis of CME in rats, determine whether it can restrain myocardial inflammation and apoptosis, and alleviate CME-induced myocardial injury.MethodsWe split 40 Sprague-Dawley (SD) rats into CME, CME + HUK, CME + HUK + LY294002 (CME + HUK + LY), and sham operation groups randomly (10 animals in each group). The dosage of HUK was 0.016 PNA/kg/day. Also, 42μm inert plastic microspheres were injected into the left ventricle of rats to establish the CME model. Notably, rats in the CME+HUK+LY group were injected 10 mg/kg of LY294002 (a particular inhibitor of PI3K) intraperitoneally 30 minutes before modeling. We measured cardiac function 12 hours after the operation. Besides, the serum of myocardial injury biomarkers and myocardial inflammation, as well as apoptosis-related genes were measured, the myocardial histopathological examination was also performed.ResultsOur results indicated that CME induced myocardial inflammation and apoptosis, also caused myocardial infarction. HUK mainly activated PI3K/Akt/FoxO1 signal transduction, effectively reducing myocardial inflammation, apoptosis, and myocardial infarction area and improving CME-induced myocardial injury. In addition, these cardioprotective effects can be reduced by PI3K specific inhibitor LY294002, suggesting that the above protective effects may be related to the process of activation of the PI3K/ Akt /FoxO1 axis.ConclusionOur findings revealed that HUK might restrain myocardial inflammation and apoptosis by activating the PI3K/Akt/FoxO1 axis, thus ameliorating CME-induced myocardial injury.