Local application of rapamycin inhibits neointimal hyperplasia in experimental vein grafts

Schachner, Thomas; Zou, Yping; Oberhuber, Alexander; Tzankov, Alexandar; Mairinger, Thomas; Laufer, Günther; Bonatti, Johannes

doi:10.1016/j.athoracsur.2003.10.008

Cited by 81 publications

(53 citation statements)

References 36 publications

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“…Schachner et al (15) have infl uenced the formation of intimal hyperplasia by local application of sirolimus (rapamycin) in vein-to-artery implantation model in mouse. They observed association between reduction of vein graft disease and decreased amount of infi ltration of adventitial layer by CD8 + cells.…”

Section: Discussionmentioning

confidence: 99%

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Tacrolimus inhibits intimal hyperplasia in arterialised veins in rats

Varga¹,

Matia²,

Lodererová³

et al. 2012

BLL

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Abstract:Objectves: We investigated whether tacrolimus (FK506) can inhibit neointimal formation in arterialised vein grafts in rats. Methods: Lewis iliolumbar veins were implanted into the abdominal aorta of isogeneic rats. Animals in the treatment groups had daily intramuscular injections of tacrolimus at 0.2 mg/kg (group B) and 0.1 mg/kg (Group C), respectively. The control group A had no treatment. Light microscope evaluations of arterialised vein grafts were performed 30 days after operation. We determined the presence of endothelial cells, the thickness of intima and media, and the degree of infi ltration by MHC class II positive, CD4 positive, and CD8 positive cells into the adventitia. Results: The intimal thickness in group B (5.0±1.0 μm) was statistically lower (P < 0.05) when compared to group C (7.0±3.0 μm). The intimal thickness in untreated group A (12.7±7.0 μm) was statistically higher (P < 0.01) when compared to both treated groups B and C, respectively. The medial thickness and degree of adventitial infi ltration by MHC class II positive, CD8 positive, and CD4 positive cells did not differ between groups. Conclusion: Treatment with tacrolimus (FK506) showed a dose dependant inhibition of neointimal hyperplasia in arterialised vein grafts in rats (Tab. 1, Fig. 3, Ref. 22). Full Text in free PDF www.bmj.sk.

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Section: Discussionmentioning

confidence: 99%

“…Tacrolimus (FK506) and sirolimus (rapamycin) are macrolide antibiotics with immunosuppressive and both anti-proliferative and anti-infl ammatory activity commonly used in transplanted patients after solid organ transplantation (14,15). Tacrolimus is less potent than sirolimus for inhibiting vascular smooth muscle cell proliferation or migration (16).…”

mentioning

confidence: 99%

Tacrolimus inhibits intimal hyperplasia in arterialised veins in rats

Varga¹,

Matia²,

Lodererová³

et al. 2012

BLL

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“…23 It is not known which one of these various affects is the main factor in adhesion formation, however, it is probable that it occurs as a result of their cumulative affect In some studies, sirolimus was applied topically around the vein grafts. These studies revealed a lower degree of neointimal hyperplasia in the venous grafts in the subjects who received topical sirolimus 25 In this study, the sirolimus applied may lead to the inhibition of intimal hyperplasia in especially the anastomosis area in the long term As this study reveals, sirolimus significantly decreases the adhesion formation between vascular grafts and peripherical tissues. Therefore, we believe further research is required on this subject both to empirically confirm our findings and to go beyond to explain the mechanisms of action.…”

Section: Discussionmentioning

confidence: 70%

“…[19][20][21][22] Rapamycin inhibits cell proliferation of connective tissue origin 23,24 by blocking the cell cycle in the G 1 and S phases, inhibiting cell proliferation. Additionally, sirolimus is reported to negatively affect wound healing There are studies reporting that it prevents intimal hyperplasia when applied topically around venous grafts 25 and that it also inhibits proliferation of smooth muscle cells and inflicts an anti-inflammatory effect on vessel walls. [26][27][28][29][30] Sirolimus inhibits the mitogenic affect of fetal calf serum in primary endothelial cell cultures and it is a potent inhibitor of cell proliferation mediated by growth factor.…”

Section: Discussionmentioning

confidence: 99%

Efficiency of sirolimus in prevention of adhesions around vascular grafts

Kanko¹,

Özbudak²,

Ozerdem³

et al. 2006

Nigerian Journal of Surgical Research

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Background: Adhesions due to the reactions caused by the grafts used in the primary vascular operation can lead to various problems when a secondary operation is necessary. These problems include: bleeding, injuries to neighboring organs sand complications occurring due to a prolonged operation. We investigated the affects of sirolimus, which has antiproliferative effects on vascular adhesions. Methods: The abdominal aortae of rats were explored and abrasions inflicted. Following the fixation of a PTFE (Polytetra floroetilen) graft on the abdominal aorta, rapamycin (sirolimus) was applied (in powder form) on the grafts of the study group. Four weeks later a laparotomy was done and the adhesions developed were evaluated. Results: In the study group the adhesions were determined to be fewer in number and milder in severity. Severe adhesion were noted in the control group. Conclusions: Therefore, sirolimus applied around the prosthesis in vascular operations, was determined to be effective in preventing possible adhesions.

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“…Rapamycin encapsulated with several surface-active agents has demonstrated good antiproliferative efficacy in vascular transplantation when locally applied. [18][19][20] However, external application of antiproliferative drugs to the vessel is suspected to affect ambient normal tissues. The ideal route of administration needs to be explored.…”

Section: Introductionmentioning

confidence: 99%

Pretreatment with intraluminal rapamycin nanoparticle perfusion inhibits neointimal hyperplasia in a rabbit vein graft model

Cao²,

Zhang³

et al. 2010

IJN

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Purpose: Poly lactic-co-glycolic acid nanoparticles (PLGA-NP) are widely used as a biodegradable biomaterial in medicine. Rapamycin-eluting stents have been used for prevention of restenosis during surgery. This study investigated the effect of pretreatment with intraluminal perfusion of carbopol-encapsulated rapamycin-loaded PLGA nanoparticles (RAP-PLGA-NP) on neointimal hyperplasia in a rabbit vein graft model. Methods: A segment of common carotid artery was replaced with a segment of external jugular vein in 60 rabbits which were then separated into four treatment groups, ie, Group 1, in which vein grafts were pretreated with intraluminal RAP-PLGA-NP perfusion, Group 2 in which vein grafts underwent equivalent empty vehicle (PLGA-NP) perfusion, Group 3, in which vein grafts received no treatment, and Group 4, which served as a sham operation group receiving normal vein contrast. On postoperative day 28, the grafts and normal veins were harvested for histologic examination, flow cytometry analysis, and high-performance liquid chromatography measurement. Results: Compared with Group 1, the intima of the grafts were thickened, the ratio of intimal area to vessel area increased, and the collagen volume index of the vein grafts increased significantly in Groups 2 and 3. The cell proliferation index in Group 1 (21.11 ± 3.15%) was much lower than that in Group 2 (30.35 ± 2.69%) and in Group 3 (33.86 ± 8.72%). By highperformance liquid chromatography measurement, retention of rapamycin was detected in Group 1 (11.2 ± 0.37 µg/10 mg) 28 days after single drug perfusion. Conclusion: Pretreatment with intraluminal RAP-PLGA-NP perfusion may inhibit neointimal hyperplasia in vein grafts by penetrating into local tissue and limiting cell proliferation.

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Local application of rapamycin inhibits neointimal hyperplasia in experimental vein grafts

Cited by 81 publications

References 36 publications

Tacrolimus inhibits intimal hyperplasia in arterialised veins in rats

Tacrolimus inhibits intimal hyperplasia in arterialised veins in rats

Efficiency of sirolimus in prevention of adhesions around vascular grafts

Pretreatment with intraluminal rapamycin nanoparticle perfusion inhibits neointimal hyperplasia in a rabbit vein graft model

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