Colchicine Inhibits Intimal Hyperplasia and Leukocyte VEGF Expression in Dogs

Background

Restenosis due to intimal hyperplasia following percutaneous transluminal angioplasty limits its long-term efficacy. We evaluated the effect of colchicine on the development of intimal hyperplasia following balloon angioplasty and on the vascular endothelial growth factor (VEGF) expression in leukocytes.

Material and methods

Adult dogs underwent balloon angioplasty of the right iliofemoral artery. Group 1 served as control, while groups 2 and 3 (six animals per group) received 0.1 and 0.5 mg/kg/d of colchicine p.o., respectively, starting 2 d before angioplasty and continued for 14 d. Before angioplasty and at day 14, blood samples were collected for drug toxicity analysis and the determination of leukocyte expression of VEGF. Animals were euthanized and iliofemoral arteries were perfusion fixed in situ and processed for histological and morphometric analysis.

Results

Balloon angioplasty without colchicine resulted in 446% (P < 0.001), 111% (P = 0.7), and 267% (P < 0.001) increase in intimal and medial thickness and intima/media ratio compared with contralateral uninjured iliofemoral arteries. Low-dose and high-dose colchicine resulted in 32% and 58% reduction in intima/media ratio, respectively (both P < 0.001). VEGF expression in leukocytes of control group was up-regulated (40%), but was down-regulated by 12% and 55%, respectively, in low-dose and high-dose colchicine groups at 2 wk after angioplasty compared with preangioplasty expression. The results of complete blood count and serum transaminases and creatinine were within normal range.

Conclusion

This study demonstrates that oral colchicine for 2 wk significantly reduces intimal hyperplasia following balloon angioplasty in dogs through down-regulation of leukocyte VEGF expression and without apparent toxicity.

Key Words: intimal hyperplasia, colchicine, vascular endothelial growth factor