Role of Vitamin C in Cardioprotection of Ischemia/Reperfusion Injury by Activation of Mitochondrial K_ATP Channel

Abstract

How to provide effective prevention and treatment of myocardial ischemia/reperfusion (I/R) injury and study of the mechanism underlying I/R injury are hotspots of current research. This study aimed to elucidate the effect and cardioprotective mechanism of vitamin C (VC) on myocardial I/R injury. Our study introduced two different I/R models: I/R in vitro and oxygen-glucose deprivation/recovery (OGD/R) in primary neonatal rat cardiac myocytes. We used the mitochondrial permeability transition pore (mPTP) opener lonidamine (LND) and the mitochondrial K ATP (mitoK ATP ) channel inhibitor 5-hydroxydecanoate (5-HD) to analyze the underlying mechanisms. We found that post-treatment with VC decreased I/R injury in our models. Post-treatment with VC significantly decreased I/R-induced injury, attenuated apoptosis, and maintained the functional integrity of mitochondria via alleviation of Ca 2 overload, reactive oxygen species burst, inhibition of the opening of mPTP, and prevention of mitochondrial membrane potential (ΔΨm) depolarization. VC post-treatment increased the phosphorylation of Akt and glycogen synthase kinase (GSK)-3β. The present results demonstrate that VC might protect the myocardium from I/R-induced injury by inhibiting the mPTP opening via activation of mitoK ATP channels. VC mediates cardioprotection via activation of the phosphatidyl inositol 3-kinase (PI3K)-Akt signaling pathway. These findings may contribute toward the development of novel strategies for clinical cardioprotection against I/R injury. Key words vitamin C (VC); ischemia/reperfusion (I/R) injury; ischemic post-treatment; mitochondrial K ATP (mitoK ATP ) channelIn recent years, cardiovascular disease has become a great threat to human life and health. Prolonged myocardial ischemia can cause tissue damage and even cell death. A key treatment of coronary heart disease is blood reperfusion of the myocardium. However, restoration of blood supply followed by myocardial cell function and structural damage results in a pathophysiological state known as ischemia/reperfusion (I/R) injury.1) The reduction occurrence of I/R injury has become a focus of current research.In 1986, Murry first put forward a self-defensive protective mechanism of the myocardial cell known as myocardial ischemia preadaptation (ischemic preconditioning; IPC), and transient ischemic preconditioning can improve myocardial ischemia and reperfusion of longer than damage tolerance ability.2) However, ischemic preconditioning poses challenges including safety and operability, and individual differences of clinical application of IPC is restricted. Thus, several studies have proposed drug post-treatment (pharmacological preconditioning; PPC), namely the simulation of IPC via a variety of drugs result in less I/R injury. 3)In myocardial I/R injury, the integrity of the mitochondrial membrane and its functions have undergone major changes, such as depolarization of the mitochondrial membrane potential (ΔΨm), interruption of mitochondrial respiratory chain electron transfer, inhibi...

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Bioactive food and exercise in chronic kidney disease: Targeting the mitochondria

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Respiratory chain signalling is essential for adaptive remodelling following cardiac ischaemia

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