INCREASE IN MEGAKARYOCYTE SIZE AND PLOIUY PRECEDES ACCELERATION OF ATHEROGENESIS IN THE HYPERCHOLESTEROLAEMIC RABBIT
Platelet derived growth factor(s) probably synthesized by the megakaryocyte are important in atherogenesis. In a pilot study destruction of the circulating platelets was induced by injection of goat serum containing a specific platelet antibody (APS) to rabbits fed a high cholesterol diet (2g per day) for 12 weeks. Seven days after APS the percentage of atheroma in the aorta measured by planimetry was increased in these animals compared to control animals on the same diet that had been injected with goat serum (GS) 7 days before. In a new study 15 pairs of male litter mate rabbits on high cholesterol diet were randomised in pairs to treatment with either APS or GS. Five pairs of animals were killed 18 hours after the injection, 5 pairs 4 days after and 5 pairs 7 days after the injection and the platelet count, mean platelet volume, megakaryocyte nuclear, cytoplasmic and total size, megakaryocyte DNA distribution and the percentage of atheroma in the aorta were measured. Comparison of these variables between the 2 groups revealed the following statistically significant findings (p<0.05) : 18 hours after the injection the platelet count was decreased and the mean platelet volume increased in the APS group. At day 4 the platelet count, megakaryocyte nuclear, cytoplasmic and total size and the megakaryocyte DNA content were increased in the APS group. At day 7 the platelet count and the percentage of the atheroma were higher in the APS group. Since platelets produced by big megakaryocytes with high DNA content are more reactive than normal platelets, we suggest that the acceleration of atheroma formation demonstrated 7 days after APS is caused by the large number of platelets with possible high concentrations of growth factor(s) derived from the large megakaryocytes with increased DNA content.