Accumulation of cholesterol ester in cultured smooth muscle cells of congenital hypercholesterolemic (WHHL) rabbits treated with normal and WHHL rabbit plasma LDL.

The DNA content, thymidine incorporation into DNA, and free and esterified cholesterol contents of cultured aortic smooth muscle cells (SMCs) of normal and WHHL rabbits were compared. In the first series of experiments, 5 groups of cultured normal rabbit aortic SMCs were compared: control cells and cells treated with LDL from normolipemic rabbit plasma (LDLN) and (DL from hypercholesterolemic rabbit plasma (LDLW), LDLN plus esterastin and LDLW plus esterastin. In the second series, the same groups of hereditable hypercholesterolemic WHHL rabbit aortic SMCs were compared. Results obtained with normal aortic SMCs showed that internalization of LDLW was higher than that of LDLN. LDLW was also more effective than LDLN for elevating thymidine incorporation into DNA. LDLW plus esterastin caused increases of 5, 7 and 3 times the control values in thymidine incorporation, and esterified and free cholesterol contents of the cells, respectively. In the control groups, thymidine incorporation into DNA of WHHL SMCs was 12 times more than that into the normal cells, and the free cholesterol content of WHHL cells was twice that of normal cells. Addition of LDLN caused further increases in thymidine incorporation and the esterified and free cholesterol contents of the cells. Esterastin had only a slight effect on these extremely high values. LDLW itself had no effect except that when added with esterastin it increased the cholesterol ester content of WHHL cells. The results are discussed with respect to metabolic differences between cultured aortic SMCs of normal and WHHL rabbits, and LDLs prepared from normal and hypercholesterolemic (WHHL) rabbit plasma.