Cardioprotective Effect of Secretory Leukocyte Protease Inhibitor (SLPI) Partially Require Association with Cardiac Annexin A2 (AnxA2)

Ischemic heart disease (IHD) is the leading cause of death globally.Novel therapeutic interventions are being developed to reduce the rates of death and disease.Previous studies have demonstrated that secretory leukocyte protease inhibitor (SLPI) has a cardioprotective effect on myocardial ischemia/reperfusion (I/R) injury.Annexin A2 (ANXA2), a negatively charged phospholipid-binding protein, has been proven to be involved in the anti-apoptotic activity of SLPI.Nevertheless, the correlation between cardiac ANXA2 and SLPI, as well as their role in the cardioprotective effects of SLPI against hypoxia/reoxygenation (H/R) injury, has not been investigated.The hypothesis of this study is that the expression of ANXA2 in ventricular myocytes and ventricular tissue, as well as the association and significance of the cardiac ANXA2-SLPI complex, play a role in protecting against in vitro hypoxia/reoxygenation (H/R) damage in rat cardiac myoblast (H9c2) cells.The results indicated that ANXA2 was expressed in ventricular cardiomyocytes and tissue.Immunoprecipitation analysis demonstrated that cardiac ANXA2 has the ability to interact with SLPI.Prior administration of anti-ANXA2 before treatment with recombinant human SLPI resulted in a considerable impairment of the cardioprotective efficacy of SLPI against in vitro H/R injury.The results were also observed in an anti-protease-deficient mutant of SLPI, indicating that the direct impact of SLPI relies on its interaction with ANXA2.This work presents novel molecular evidence supporting the link between cardiac ANXA2 and SLPI and the cardioprotective effect of SLPI against H/R damage.These findings have important implications for the potential therapeutic uses of SLPI in the future.