Clonal nature of atherosclerotic plaques

The clonal nature of atherosclerotic plaques has been examined in diet-induced atherosclerosis of interspecies hybrid hare females (Lepus timidus (female) X Lepus europaeus (male], which exhibit genetic mosaicism with respect to glucose-6-phosphate dehydrogenase (G6P-D). Four diet groups have been used: control pellet diet, hyperlipemic (HL) diet, and HL diet supplemented with two different concentrations of 25-hydroxycholesterol. Lesion and nonlesion tissue samples and primary cultures developed from similar samples were used to determine the G6P-D variant patterns. A close correlation was observed, using regression analysis, between the in vivo and the in vitro phenotype. As has been reported earlier by us, most lesions in this animal model were heterozygous and the few homozygous areas recorded were all in the diet groups supplemented with 25-hydroxycholesterol. However, in tissue culture, homozygosity appeared with greater frequency, still of the T phenotype. In order to rule out maternal dominance as a factor, preliminary experiments involving G6P-D analysis have been carried out using tissue samples and cell cultures derived from a reverse cross. These also show a strong bias toward the T phenotype. The studies presented here highlight the difficulties in interpretation using G6P-D analysis as the sole criterion to determine the clonal nature of the atherosclerotic plaques. It also seems likely that the kind of diet given to induce atherosclerosis might influence the nature of the clonal growth. Studies using transfection are essential to determine whether transforming sequences are present in atherosclerotic lesions.