IMR Press / FBL / Volume 27 / Issue 10 / DOI: 10.31083/j.fbl2710298
Open Access Original Research
Human Urinary Kallidinogenase Pretreatment Inhibits Myocardial Inflammation and Apoptosis after Coronary Microembolization by Activating PI3K/Akt/FoxO1 Axis
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1 Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Cardiovascular Institute, 530021 Nanning, Guangxi, China
2 Department of Cardiology, The First People Hospital of Nanning & The Fifth Affiliated Hospital of Guangxi Medical University, 530016 Nanning, Guangxi, China
3 The First Clinical College, Guangxi Medical University, 530021 Nanning, Guangxi, China
4 Guangxi Key Laboratory of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention, 530021 Nanning, Guangxi, China
5 Innovative Research Team of Guangxi Natural Science Foundation, 530021 Nanning, Guangxi, China
*Correspondence: (Lang Li)
These authors contributed equally.
Academic Editor: Graham Pawelec
Front. Biosci. (Landmark Ed) 2022, 27(10), 298;
Submitted: 18 July 2022 | Revised: 28 August 2022 | Accepted: 6 September 2022 | Published: 31 October 2022
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

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.

human urinary kallidinogenase
coronary artery microembolization
myocardial inflammation
2018GXNSFGA281006/Innovative Research Team Projec of Guangxi Natural Science Foundation
82170349/National Natural Science Foundation of China
Fig. 1.
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