Short-term Statin Treatment Does Not Prevent Ischemia and Reperfusion-induced Endothelial Dysfunction in Humans

Statins are known to have cholesterol-independent pleiotropic effects, such as upregulation of the enzyme ecto-5'-nucleotidase. These effects may contribute to the protective effect of statins against ischemia and reperfusion (IR). Interestingly, pleiotropic effects have been shown to differ between hydrophilic and lipophilic statins. Flow-mediated dilation (FMD) represents a largely nitric oxide-mediated, endothelium-dependent dilation and has been shown to decrease after exposure to IR in humans. FMD has been validated to study (pharmacological) interventions in IR injury. We examined the effect of a short-term (3-7 days) statin pretreatment on brachial artery endothelial function before and after IR, and whether the effect on brachial artery endothelial function differs between rosuvastatin (hydrophilic statin) and atorvastatin (lipophilic statin). Our results show that IR significantly decreases FMD; however, statin pretreatment did not alter the effect of IR on FMD (irrespective of treatment duration or type of statin used). This experiment suggests that the cardioprotective effects of statins (both lipophilic and hydrophilic) against IR are not mediated through preservation of endothelial function.