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Abstract 11972: Ivabradine Attenuates Hypoxia/Reoxygenation-Induced Excessive Autophagy in H9c2 Cardiomyocyte by Modulation of the PI3K/Akt/mTOR Pathway


 Introduction:
 Despite recent advances in resuscitation techniques, the mortality associated with survival from cardiac arrest (CA) still remains low. Cardiovascular ischemia/reperfusion injury (IRI) is one of the primary pathophysiology involved.
 
 
 Hypothesis:
 We assessed the hypothesis that ivabradine could attenuate hypoxia/reoxygenation injury of H9c2 cardiomyocytes by inhibiting excessive autophagy through PI3K/Akt/mTOR Pathway.
 
 
 Methods:
 Cultured H9c2 were randomly divided into 3 groups: CON (normoxia), H/R (hypoxia reoxygenation) and IVA. The IVA was divided into 4 subgroups, in which H9c2 were treated with or without ivabradine(20μM or 100μM) or PI3-kinase inhibitor LY294002(10μM) for 12 hours and then subjected to 12 hours of hypoxia and 24 hours of reoxygenation. Hypoxia was achieved by a hypoxia chamber filled with 5%CO
 2
 and 95% N
 2
 at 37°C. Cell viability were measured with CCK-8 assay kits. Cell autophagy was assessed by transmission electron microscopy (TEM). The expressions of autophagy marker protein (LC3, Beclin-1), PI3K, Akt and mTOR were determined by Western-blot assay.
 
 
 Results:
 A decrease of cell viability and an increase formulation of autophagosomes /autophagy lysozymes occurred after H/R. Significant improvement was noted in cells treated with ivabradine compared to H/R(Figure 1). Ivabradine promoted pmTOR/mTOR expression and lower expressions of LC3II/LC3I and Beclin 1. LY294002 antagonized the effects of ivabradine on antophagy (Figure 2).
 
 
 Conclusions:
 Ivabradine could protect H9c2 against H/R injury via inhibiting excessive autophagy through PI3K/Akt/mTOR pathway.
 
 
 
