ALTERATIONS OF RABBIT AORTIC SMOOTH-MUSCLE CELL-PROLIFERATION IN DIABETES-MELLITUS

Objective: Diabetes mellitus is a known risk factor for atherosclerosis. Because initiation and/or progression of the atherosclerotic process is associated with alterations in vascular smooth muscle cell growth and differentiation, the present studies were conducted to evaluate the effect of diabetes mellitus on the proliferative behaviour of cultured aortic smooth muscle cells. Methods: Male New Zealand White rabbits were made diabetic with a single intravenous injection of alloxan monohydrate (100 mg.kg-1) in saline. Primary cultures of smooth muscle cells were established from thoracic aortic segments of control and diabetic rabbits and used to develop multiple cell strains. The proliferative capability of secondary cultures was determined by measurements of [H-3]-thymidine incorporation into DNA, cell counts, and protein content in control and diabetic cultures. The serum dependence of cellular growth was evaluated by incubation of cultured cells in growth medium supplemented with various fetal calf serum concentrations. Results: Cultures of diabetic origin incorporated thymidine to a greater extent than control cultures. Although the efficiency of cell attachment was not different between control and diabetic cells, diabetic cells had a shorter population doubling time than control cells [41.08(SEM 4.15) h v 58.08(6.79) h] and achieved higher final densities than control cultures. The serum dependence of smooth muscle cell cultures for viability and growth was different between the two groups. Conclusions: These findings support the hypothesis that diabetes induces changes in vascular smooth muscle cell proliferation which may be associated with the onset or progression of the atherogenic process observed in diabetes.