Simvastatin reduces reperfusion injury by modulating nitric oxide synthase expression: an ex vivo study in isolated working rat hearts

Abstract

In this model, in the absence of perfusing granulocytes, the acute administration of a pharmacologically relevant simvastatin concentration reduces ischemia-reperfusion injury and prevents coronary endothelial cell and cardiomyocyte damage by cholesterol-independent, NO-dependent mechanisms.

Statin and resveratrol in combination induces cardioprotection against myocardial infarction in hypercholesterolemic rat

“…Statins have also been shown to have dose dependent effects on VEGF expression [18]. The upregulation of eNOS-NO system by statin, has been proposed as a mechanism underlying how statins protect ischemic/reperfused myocardium [5,19]. Despite several developments of novel approaches to cholesterol reduction, statin therapy remains the mainstay of cholesterol-lowering therapy.…”

The effect of acute simvastatin administration on the severity of arrhythmias resulting from ischaemia and reperfusion in the canine: Is there a role for nitric oxide?

“…Considering the electrophysiological differences between the ischaemia-induced and the reperfusion-induced arrhythmias (Wit and Janse, 2001), and that, in this latter, the products of the oxidative stress and the calcium overload (Opie and Coetzee, 1988) play a mandatory role, it seems more than likely that simvastatin through an NO-dependent way (Di Napoli et al, 2001) reduces superoxide production and hence the occurrence of VF during reperfusion. Consequently, this protection disappears by inhibiting the formation of NO.…”

The role of PPAR in myocardial response to ischemia in normal and diseased heart

“…By inhibition of the enzyme HMG-CoA reductase statins have been reported to prevent the synthesis of isoprenoid intermediates of cholesterol biosynthesis pathway involved in posttranslational modification of small GTP-binding proteins, such as Ras, Rho, and Rac, which modulate a variety of cellular processes (Takemoto and Liao 2001), e.g., oxidative stress and inflammation (Van Linthout et al 2007;Zhou et al 2008;Adameová et al 2009b), vascular endothelial dysfunction (Takemoto and Liao 2001) and the outcome of myocardial response to I/R (Adameová et al 2006(Adameová et al , 2009a. It is hypothesized that in the myocardium, treatment with statins induces preconditioning-like effects attributed to up-regulation of "survival" pathways, such as PI3K/Akt, ERK1/2 and eNOS (Di Napoli et al 2001;Efthymiou et al 2005;Merla et al 2007). In addition, in the hearts of normocholesterolemic rats exposed to I/R after 5-days treatment with simvastatin, a remarkable elevation in PPAR-α gene expression coupled with an enhanced protein expression (3.3-fold and 2-fold increase in mRNA and protein levels, respectively) was observed in the myocardium of these animals at baseline and after 30-min global ischemia and 2-h reperfusion.…”