Neointimal hyperplasia persists at six months after sirolimus-eluting stent implantation in diabetic porcine.
BACKGROUND
Observational clinical studies have shown that patients with diabetes have less favorable results after percutaneous coronary intervention compared with the non-diabetic counterparts, but its mechanism remains unclear. The aim of this study was to examine the changes of neointimal hyperplasia after sirolimus-eluting stent (SES) implantation in a diabetic porcine model, and to evaluate the impact of aortic inflammation on this proliferative process.


METHODS
Diabetic porcine model was created with an intravenous administration of a single dose of streptozotocin in 15 Chinese Guizhou minipigs (diabetic group); each of them received 2 SES (Firebird, Microport Co, China) implanted into 2 separated major epicardial coronary arteries. Fifteen non-diabetic minipigs with SES implantation served as controls (control group). At 6 months, the degree of neointimal hyperplasia was determined by repeat coronary angiography, intravascular ultrasound (IVUS) and histological examination. Tumor necrosis factor (TNF)-alpha protein level in the aortic intima was evaluated by Western blotting, and TNF-alpha, interleukin (IL)-1beta and IL-6 mRNA levels were assayed by reverse transcription and polymerase chain reaction.


RESULTS
The distribution of stented vessels, diameter of reference vessels, and post-procedural minimal lumen diameter were comparable between the two groups. At 6-month follow-up, the degree of in-stent restenosis (40.4 +/- 24.0% vs. 20.2 +/- 17.7%, p < 0.05), late lumen loss (0.33 +/- 0.19 mm vs. 0.10 +/- 0.09 mm, p < 0.001) by quantitative angiography, percentage of intimal hyperplasia in the stented area (26.7 +/- 19.2% vs. 7.3 +/- 6.1%, p < 0.001) by IVUS, and neointimal area (1.59 +/- 0.76 mm2 vs. 0.41 +/- 0.18 mm2, p < 0.05) by histological examination were significantly exacerbated in the diabetic group than those in the controls. Significant increases in TNF-alpha protein and TNF-alpha, IL-1beta and IL-6 mRNA levels were observed in aortic intima in the diabetic group.


CONCLUSIONS
Neointimal hyperplasia persisted at least up to 6 months after SES implantation in diabetic porcine, which may be partly related to an exaggerated inflammatory response within the blood vessel wall. Our results provide theoretical support for potential direct beneficial effects of anti-diabetic and anti-inflammation medications in reducing the risk of restenosis after stenting.
Zhang
Qi
Q
Department of Cardiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China. zhangqnh@yahoo.com
Lu
Lin
L
Pu
LiJin
L
Zhang
RuiYan
R
Shen
Jie
J
Zhu
ZhengBing
Z
Hu
Jian
J
Yang
ZhenKun
Z
Chen
QiuJin
Q
Shen
WeiFeng
W
D000818:Animals; D002408:Catheters, Indwelling; D003331:Coronary Vessels / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D003925:Diabetic Angiopathies / Q000628:therapy*; D004195:Disease Models, Animal; D006965:Hyperplasia / Q000139:chemically induced; D008297:Male; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects*; D015607:Stents; D013552:Swine; D017539:Tunica Intima / Q000473:pathology*
D020123:Sirolimus