Effect of diet-induced hypercholesterolemia on proteoglycan metabolism in guinea pig megakaryocytes and platelets.

Proteoglycan metabolism was evaluated in megakaryocytes and platelets from guinea pigs fed a 1% cholesterol diet for 3 or 7 weeks. The animals were injected with a single dose of [35S]sulfate at the end of the feeding period, and megakaryocytes and platelets were isolated after 3 hours and then daily for 4 days thereafter. Proteoglycans were extracted from the cells of each animal and analyzed by ion-exchange chromatography, gel filtration, and electrophoresis. The maximal labeling of platelets occurred 2 days after [35S]sulfate injection as compared with 3 days in controls. A proteoglycan that eluted at Kav 0.2 from the Sepharose CL-6B column appeared 1 day after labeling. Additional proteoglycans of Kav 0.15 appeared at subsequent time points. The labeling profile for cholesterol-fed animals was unchanged from 2-4 days, unlike profiles from controls, which had exhibited a gradual increase in mean proteoglycan size. Thus, the progressive change in size of proteoglycans synthesized during normal megakaryocyte maturation was altered. The mean chain length of the proteoglycan-associated glycosaminoglycans from cholesterol-fed animals was increased relative to that of controls. In conjunction with the twofold increase in mean megakaryocyte size induced by cholesterol feeding in guinea pigs, the changes in proteoglycan synthesis suggest a state of stimulated megakaryocytopoiesis.