title: Rosuvastatin attenuates angiotensin II-induced neointimal formation after stent implantation in the rat.
abstract: OBJECTIVE
  We investigated the efficacy of oral rosuvastatin treatment to reduce in-stent neointima formation, both in the absence and presence of high levels of the proproliferative substance angiotensin II (Ang II).
  
  
  BACKGROUND
  Drawbacks of current drug-eluting stents include inhibition of reendothelialization, induction of abnormal coronary endothelial function, and, most importantly, late in-stent thrombosis. Statin treatment might be a more subtle approach, with known beneficial vascular effects.
  
  
  METHODS
  Wistar rats were allocated to four treatment groups by two consecutive randomization steps: one to allocate rosuvastatin 0.047% (wt/wt) supplemented rat chow, and one to implant an osmotic minipump releasing Ang II (200 ng/kg). Stents were implanted in the abdominal aorta in all groups. After 4 weeks, in-stent neointima formation and vascular function in the thoracic aorta were determined.
  
  
  RESULTS
  In the absence of Ang II, rosuvastatin reduced neointima formation by 23% as compared with control (0.66+/-0.06 versus 0.51+/-0.02 mm2; P<0.05). The presence of Ang II enhanced neointimal area by 30%. This was inhibited to the same extent by rosuvastatin (0.88+/-0.06 versus 0.67+/-0.03 mm2; P<0.05). In parallel, rosuvastatin improved endothelial-dependent vasodilatation, both in the presence and absence of high levels of Ang II.
  
  
  CONCLUSIONS
  Ang II infusion increases in-stent neointima formation and decreases endothelial function. We now provide evidence that rosuvastatin effectively inhibits in-stent neointima formation and in parallel improves endothelial dilator function, both in the presence and absence of high Ang II levels.
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Pim
authors.initials: P
authors.lastname: van der Harst
authors.forename: Hendrik C
authors.initials: HC
authors.lastname: Groenewegen
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: Roks
authors.forename: Hendrik
authors.initials: H
authors.lastname: Buikema
authors.forename: Felix
authors.initials: F
authors.lastname: Zijlstra
authors.forename: Wiek H
authors.initials: WH
authors.lastname: van Gilst
authors.forename: Bart J G L
authors.initials: BJ
authors.lastname: de Smet
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D005464:Fluorobenzenes / Q000494:pharmacology*; D006083:Graft Occlusion, Vascular / Q000517:prevention & control*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006965:Hyperplasia; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D000068718:Rosuvastatin Calcium; D015607:Stents; D013449:Sulfonamides / Q000494:pharmacology*; D017539:Tunica Intima / Q000187:drug effects*
chemical_list: D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000804:Angiotensin II; D000068718:Rosuvastatin Calcium