title: Short-term statin treatment does not prevent ischemia and reperfusion-induced endothelial dysfunction in humans.
abstract: 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.
authors: Department of Pharmacology-Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors: Constantijn W
authors: CW
authors: Wouters
authors: Kimberley E
authors: KE
authors: Wever
authors: Inge
authors: I
authors: Bronckers
authors: Maria T E
authors: MT
authors: Hopman
authors: Paul
authors: P
authors: Smits
authors: Dick H J
authors: DH
authors: Thijssen
authors: Gerard A
authors: GA
authors: Rongen
mesh_terms: D015720:5'-Nucleotidase / Q000096:biosynthesis; D000293:Adolescent; D000328:Adult; D000069059:Atorvastatin; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D005464:Fluorobenzenes; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin; D015720:5'-Nucleotidase