TY - JOUR
T1 - Long-term effect of stents eluting 6-mercaptopurine in porcine coronary arteries
AU - Ruiter, Matthijs S.
AU - Doornbos, Albert
AU - de Waard, Vivian
AU - de Winter, Robbert J.
AU - Attevelt, Nico J. M.
AU - Steendam, Rob
AU - de Vries, Carlie J. M.
PY - 2016
Y1 - 2016
N2 - Background: Drug-eluting stents (DES) have dramatically reduced restenosis rates compared to bare metal stents and are widely used in coronary artery angioplasty. The anti-proliferative nature of the drugs reduces smooth muscle cell (SMC) proliferation effectively, but unfortunately also negatively affects endothelialization of stent struts, necessitating prolonged dual anti-platelet therapy. Cell-type specific therapy may prevent this complication, giving rise to safer stents that do not require additional medication. 6-Mercaptopurine (6-MP) is a drug with demonstrated cell-type specific effects on vascular cells both in vitro and in vivo, inhibiting proliferation of SMCs while promoting survival of endothelial cells. In rabbits, we demonstrated that DES locally releasing 6-MP during 4 weeks reduced in-stent stenosis by inhibiting SMC proliferation and reducing inflammation, without negatively affecting endothelialization of the stent surface. The aim of the present study was to investigate whether 6-MP-eluting stents are similarly effective in preventing stenosis in porcine coronary arteries after 3 months, in order to assess the eligibility for human application. Methods: 6-MP-eluting and polymer-only control stents (both n = 7) were implanted in porcine coronary arteries after local balloon injury to assess the effect of 6-MP on vascular lesion formation. Three months after implantation, stented coronary arteries were harvested and analyzed. Results: Morphometric analyses revealed that stents were implanted reproducibly and with limited injury to the vessel wall. Unexpectedly, both in-stent stenosis (6-MP: 41.1 +/- 10.3 %; control: 29.6 +/- 5.9 %) and inflammation (6-MP: 2.14 +/- 0.51; control: 1.43 +/- 0.45) were similar between the groups after 3 months. Conclusion: In conclusion, although 6-MP was previously found to potently inhibit SMC proliferation, reduce inflammation and promote endothelial cell survival, thereby effectively reducing in-stent restenosis in rabbits, stents containing 300 mu g 6-MP did not reduce stenosis and inflammation in porcine coronary arteries
AB - Background: Drug-eluting stents (DES) have dramatically reduced restenosis rates compared to bare metal stents and are widely used in coronary artery angioplasty. The anti-proliferative nature of the drugs reduces smooth muscle cell (SMC) proliferation effectively, but unfortunately also negatively affects endothelialization of stent struts, necessitating prolonged dual anti-platelet therapy. Cell-type specific therapy may prevent this complication, giving rise to safer stents that do not require additional medication. 6-Mercaptopurine (6-MP) is a drug with demonstrated cell-type specific effects on vascular cells both in vitro and in vivo, inhibiting proliferation of SMCs while promoting survival of endothelial cells. In rabbits, we demonstrated that DES locally releasing 6-MP during 4 weeks reduced in-stent stenosis by inhibiting SMC proliferation and reducing inflammation, without negatively affecting endothelialization of the stent surface. The aim of the present study was to investigate whether 6-MP-eluting stents are similarly effective in preventing stenosis in porcine coronary arteries after 3 months, in order to assess the eligibility for human application. Methods: 6-MP-eluting and polymer-only control stents (both n = 7) were implanted in porcine coronary arteries after local balloon injury to assess the effect of 6-MP on vascular lesion formation. Three months after implantation, stented coronary arteries were harvested and analyzed. Results: Morphometric analyses revealed that stents were implanted reproducibly and with limited injury to the vessel wall. Unexpectedly, both in-stent stenosis (6-MP: 41.1 +/- 10.3 %; control: 29.6 +/- 5.9 %) and inflammation (6-MP: 2.14 +/- 0.51; control: 1.43 +/- 0.45) were similar between the groups after 3 months. Conclusion: In conclusion, although 6-MP was previously found to potently inhibit SMC proliferation, reduce inflammation and promote endothelial cell survival, thereby effectively reducing in-stent restenosis in rabbits, stents containing 300 mu g 6-MP did not reduce stenosis and inflammation in porcine coronary arteries
U2 - https://doi.org/10.1186/s12952-016-0063-y
DO - https://doi.org/10.1186/s12952-016-0063-y
M3 - Article
C2 - 27916002
SN - 1477-5751
VL - 15
SP - 20
JO - Journal of negative results in biomedicine
JF - Journal of negative results in biomedicine
IS - 1
ER -