Colchicine reduces atherosclerotic plaque vulnerability in rabbits.

BACKGROUND AND AIMS

The anti-inflammatory agent colchicine is gaining interest as a treatment for coronary artery disease. However, the effects of colchicine in atherosclerotic animal models are mostly unknown. This study aimed to evaluate colchicine in a rabbit model of atherosclerosis.

METHODS

Twenty-two rabbits were fed a 0.5% cholesterol-enriched diet for 10 weeks and then randomized to receive either oral saline (n=11) or colchicine (350 μg/kg/day; n=11) for 6 weeks, with 0.2% cholesterol-diet during the treatment period. We performed intravascular ultrasound imaging (at start and end of treatment) and histology analyses of the descending thoracic aorta. Leucocyte activation was assessed on blood samples obtained during treatment.

RESULTS

Colchicine prevented positive aortic vascular remodelling (=0.029 placebo). This effect was even more marked at high plasma cholesterol level (third quartile of plasma cholesterol, =0.020). At high cholesterol level, both atherosclerotic plaque and media areas on histomorphology were reduced by colchicine compared to placebo (=0.031 and =0.039, respectively). Plaque fibrosis and macrophage area were reduced by colchicine (Masson's trichrome stain: =0.038; RAM-11: =0.026). The plaque vulnerability index, assessed by histology, was reduced by colchicine (=0.040). Elastin/type I collagen ratio in media was significantly higher with colchicine compared to placebo (=0.013). At a high level of plasma cholesterol, LPS challenge revealed a decrease in monocyte activation following treatment with colchicine (<0.001) and no change in the placebo group (=0.353).

CONCLUSIONS

Colchicine decreases plaque vulnerability with reductions in plaque inflammation, medial fibrosis, outward vascular remodelling and monocyte activation.