Rosuvastatin attenuates angiotensin II-induced neointimal formation after stent implantation in the rat

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.

CONCLUSION: 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.