J Korean Surg Soc.  2013 Dec;85(6):296-301. 10.4174/jkss.2013.85.6.296.

Inhibition of intimal hyperplasia by local perivascular application of rapamycin and imatinib mesilate after carotid balloon injury

• Park D
• Kim SM
• Min SI
• Ha J
• Kim IG
• Min SK

• KMID: 2212555
• DOI: http://doi.org/10.4174/jkss.2013.85.6.296

Abstract

PURPOSE
Inhibition of the intimal hyperplasia after vascular surgery is an important issue. The purpose of this study is to define whether perivascular application of rapamycin, imatinib mesylate or cysteamine can reduce intimal hyperplasia in a carotid balloon injury model.
METHODS
Each drug was mixed with 40% pluronic gel solution and was topically applied over the injured carotid artery evenly. Two or four weeks after injury, the arteries were harvested and morphometric analysis was done.
RESULTS
The medial areas were not significantly different in each group and a thinning of the media as a toxic drug effect was not observed in any treatment group. The intimal area and intima-to-media (I/M) ratio were significantly reduced in rapamycin-treated group and imatinib-treated group (P < 0.05). But cysteamine-treated group showed a trend of decrease in I/M ratio in 2 weeks, but no difference in 4 weeks.
CONCLUSION
Perivascular delivery of imatinib or rapamycin with pluronic gel attenuated the development of intimal hyperplasia. But cysteamine did not. Further studies are needed to refine the optimal drug dosages in large animal models.

Keyword

Imatinib mesylate; Rapamycin; Cysteamine; Intimal hyperplasia; Carotid artery injury

MeSH Terms

Arteries
Benzamides
Carotid Arteries
Carotid Artery Injuries
Cysteamine
Hyperplasia*
Imatinib Mesylate
Mesylates*
Models, Animal
Piperazines
Pyrimidines
Sirolimus*
Benzamides
Cysteamine
Mesylates
Piperazines
Pyrimidines
Sirolimus

Figure

• 

  Fig. 1 Comparison of the medial area. The medial areas were not significantly different in each group.

• 

  Fig. 2 Effect of rapamycin treatment. (A, B) Cross-sections of the carotid arteries in control and after local application of rapamycin. (C) Intimal area was reduced in rapamycin group. (D) Intima-to-media ratio was reduced in rapamycin group.

• 

  Fig. 3 Comparison of intimal area (A) and intima-to-media ratio (B) after local application of imatinib.

• 

  Fig. 4 Comparison of intimal area (A) and intima-to-media ratio (B) after local application of cysteamine, a transglutaminase-2 inhibitor.

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