Direct stenting limits sirolimus-eluting stent edge neointimal thickening.
OBJECTIVE
The use of sirolimus eluting stent (SES) has strongly limited the incidence of in-stent restenosis that still remains a problem at the stent edge. The aim of this study was to analyze the neointimal thickening after implantation of SES and to assess the influence of the stent implantation procedure on the neointimal thickening in the in-stent segment and at the edge of the stent in an ex-vivo model of stented human artery.


METHODS
Both balloon expandable SES and the corresponding bare metal stent (BMS) were used in a model of human mammary artery culture. Stents were implanted either directly or after predilatation (10 atm, 60 seconds) and analysis of arterial segments were performed at 28 days poststenting. Cell proliferation and neointimal thickening were assessed by immunohistochemistry, western blotting, and histomorphometry, both in the in-stent segment and at the edge of the stent. Neointimal thickening was expressed as the ratio ([neointimal area/neointimal area + media area]).


RESULTS
The in-stent neointimal thickening was dramatically inhibited in the SES group compared with the BMS group whatever the stenting technique was (predilatation: 0.22 +/- 0.05 vs 0.30 +/- 0.10; P < .04; direct stenting 0.16 +/- 0.04 vs 0.30 +/- 0.13; P <.01). This effect of SES was associated with a smallest expression of the small G protein RhoA and an increase of p27kip expression. In the BMS group, predilatation and direct stenting gave similar in-stent neointimal thickening. In contrast, in the SES group, in-stent neointimal thickening was significantly reduced when direct stenting was performed (0.16 +/- 0.04 [direct stenting] vs 0.22 +/- 0.05 [predilatation], P < .03). At the stent edge, a similar neointimal thickening was observed with both type of stent when predilatation was performed on the entire segment of the artery. Direct stenting significantly reduced the neointimal thickness at the stent edge when SES where used (0.06 +/- 0.01 [direct stenting] vs 0.19 +/- 0.06 [predilatation]; P < .001) but not in the BMS group.


CONCLUSIONS
These results confirm the efficiency of sirolimus released form SES to inhibit RhoA expression and to increase p27kip level in the arterial wall and show the benefit of direct stenting to limit the edge effect with SES.
Inserm, U533, l'institut du thorax, Université de Nantes, Nantes, France. patrice.guerin@chu-nantes.fr
Patrice
P
Guérin
Yann
Y
Gouëffic
Marie-Françoise
MF
Heymann
Paul
P
Pillet
Oussama
O
Al Habash
Dominique
D
Crochet
Pierre
P
Pacaud
Gervaise
G
Loirand
D019917:Blood Vessel Prosthesis Implantation / Q000295:instrumentation*; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D002404:Catheterization; D049109:Cell Proliferation / Q000187:drug effects*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D006801:Humans; D008323:Mammary Arteries / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery / Q000648:ultrastructure; D008670:Metals; D008855:Microscopy, Electron, Scanning; D009924:Organ Culture Techniques; D011474:Prosthesis Design; D020123:Sirolimus / Q000008:administration & dosage*; D015607:Stents; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery / Q000648:ultrastructure; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D002317:Cardiovascular Agents; D008670:Metals; D050760:Cyclin-Dependent Kinase Inhibitor p27; D020742:rhoA GTP-Binding Protein; D020123:Sirolimus