Human Urinary Kallidinogenase Pretreatment Inhibits Myocardial Inflammation and Apoptosis after Coronary Microembolization by Activating PI3K/Akt/FoxO1 Axis.

BACKGROUND

As a fatal cardiovascular complication, coronary microembolization (CME) results in severe cardiac dysfunction and arrhythmia associated with myocardial inflammation and apoptosis. Human urinary kallidinogenase (HUK) can provide a protective function for cardiomyocytes by improving microcirculation. However, the therapeutic effects and underlying mechanisms of HUK in CME-induced myocardial injury remain unclear.

AIMS

We evaluated the effect of HUK on cardiac protection in a rat model of CME and whether it could restrain myocardial inflammation and apoptosis, and alleviate CME-induced myocardial injury.

METHODS

We established the CME model by injecting 42 μm inert plastic microspheres into the left ventricle of rats in advance, then the rats were randomly and equally divided into CME, CME + HUK (the dose of HUK at 0.016 PNA/kg/day), CME + HUK + LY (the dose of LY294002 at 10 mg/kg, 30 minutes before modeling), and Sham operation groups. Cardiac function, the serum levels of myocardial injury biomarkers, myocardial inflammation and apoptosis-related genes were measured; and the myocardial histopathological examination was performed at 12 h after the operation.

RESULTS

The results revealed that HUK effectively reducing myocardial inflammation, apoptosis, and myocardial infarction area; and improving CME-induced cardiac injury by activating the PI3K/Akt/FoxO1 axis. In addition, these cardioprotective effects can be reduced by the PI3K specific inhibitor LY294002, suggesting that the aforementioned protective effects may be related to activation of the PI3K/Akt/FoxO1 axis.

CONCLUSIONS

HUK seems to control inflammatory infiltration and cardiomyocyte apoptosis significantly to improve CME-induced cardiac injury via regulating the PI3K/Akt/FoxO1 axis.