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.


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.


CONCLUSIONS
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.
Atta
Hussein M
HM
Department of Surgery, Faculty of Medicine, Minia University, El-Minia, Egypt. attahm@ems.org.eg
El-Rehany
Mahmoud A
MA
Abdel Raheim
Salama R
SR
Fouad
Rasha
R
Galal
Abdel Moneim F
AM
D000800:Angioplasty, Balloon; D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D003078:Colchicine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004285:Dogs; D015536:Down-Regulation; D005263:Femoral Artery; D015870:Gene Expression; D006965:Hyperplasia / Q000517:prevention & control*; D007962:Leukocytes / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017539:Tunica Intima / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D002317:Cardiovascular Agents; D042461:Vascular Endothelial Growth Factor A; D003078:Colchicine