The effects of heparin upon atherogenesis in the Watanabe heritable hyperlipidemic rabbit

Heparin is routinely added to vascular cell cultures to inhibit smooth muscle cell proliferation. The in vivo effects of heparin upon atherogenesis have remained controversial, however. In this experiment 13 four-month-old, heritably hyperlipidemic, Watanabe rabbits were randomly assigned to three treatment groups: 1500 U heparin, 500 U heparin, or saline. An injection protocol was followed for nine months. The rabbits were bled monthly from their marginal ear veins and plasma from these bleeds was analyzed for cholesterol and triglyceride content. At sacrifice each rabbit's aorta was sampled at 10 specific locations from the arch to the iliac bifurcation. The reduction in the area of the aorta by atherosclerotic plaque at each site was calculated using a video imaging system. Heparin injections significantly reduced mean plasma levels of cholesterol and triglycerides compared to pretreatment levels and saline injected controls. However, the magnitude of the reduction was not dose-related. The aortic luminal area occupied by atherosclerotic plaque in rabbits injected with 1500 U of heparin was significantly less (p less than .05) than in rabbits injected with saline or 500 U of heparin. Plaques from heparin-treated animals contained more fatty deposits and foam cells compared to the plaques from saline-treated rabbits which were more fibromuscular in organization. We conclude that heparin modulates the occurrence and composition of atherosclerotic plaques in this animal model of naturally occurring atherogenesis.