Abstract
Acute myocardial ischaemia/reperfusion (MI/R) injury causes severe arrhythmias with a high rate of lethality. Extensive research focus on endoplasmic reticulum (ER) stress and its dysfunction which leads to cardiac injury in MI/R Our study evaluated the effects of sulodexide (SDX) on MI/R by establishing MI/R mice models and in vitro oxidative stress models in H9C2 cells. We found that SDX decreases cardiac injury during ischaemia reperfusion and decreased myocardial apoptosis and infarct area, which was paralleled by increased superoxide dismutase and reduced malondialdehyde in mice plasm, increased Bcl‐2 expression, decreased BAX expression in a mouse model of MI/R. In vitro, SDX exerted a protective effect by the suppression of the ER stress which induced by tert‐butyl hydroperoxide (TBHP) treatment. Both of the in vivo and in vitro effects were involved in the phosphatidylinositol 3‐kinase (PI3K)/Akt signalling pathway. Inhibition of PI3K/Akt pathway by specific inhibitor, LY294002, partially reduced the protective effect of SDX. In short, our results suggested that the cardioprotective role of SDX was related to the suppression of ER stress in mice MI/R models and TBHP‐induced H9C2 cell injury which was through the PI3K/Akt signalling pathway.
Highlights
Myocardial ischaemia/reperfusion (MI/R) injury occurs when an aor‐ tic cross‐clamp is removed or a balloon is deflated, during cardiac surgery.[1]
There is no effective therapy for MI/R4 The underlying mechanisms of MI/R injury include calcium overload, free radical damage, microvascular damage and leucocyte activation,[5,6] which lead to endoplasmic reticulum (ER) and mitochondrial injury
Myocardial ischaemia/reperfusion injury induces the production of free radicals, leading to oxidative stress, denaturation, degrada‐ tion and crosslinking of proteins and polysaccharides and apoptosis of cardiomyocytes.[7]
Summary
Myocardial ischaemia/reperfusion (MI/R) injury occurs when an aor‐ tic cross‐clamp is removed or a balloon is deflated, during cardiac surgery.[1]. Phosphatidylinositol 3‐kinase (PI3K) and Akt are sig‐ nal transduction proteins critical for many aspects of cell survival, growth and apoptosis. They are reportedly involved in the patholog‐ ical processes of diverse diseases.[19] In the myocardium, PI3K/Akt in‐ directly regulates contraction of cardiac muscle, calcium channels[20] and myocardial ischaemic reperfusion.[21] It is implicated in the control of cell growth, proliferation,[22] apoptosis[23] and ER stress.[24,25] Lauver et al reported that SDX attenuates MI/R injury.[26] the relationships of SDX to myocardial injury, ER stress‐induced apoptosis and the PI3K/Akt pathway are unknown. The role of SDX in the PI3K/Akt signalling pathway was investigated using the PI3K/Akt inhibitor LY294002
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