RELATIVE CONTRIBUTIONS OF APOLIPOPROTEIN(A) AND APOLIPOPROTEIN-B TO THE DEVELOPMENT OF FATTY LESIONS IN THE PROXIMAL AORTA OF MICE

Transgenic mice expressing transgenes for both human apolipoprotein B- 100 (h-apoB) and apolipoprotein(a) [apo(a)] were fed a high-fat, ather ogenic diet for 14 weeks to examine the effect of lipoprotein(a) [Lp(a )] on the development of aortic fatty lesions. The extent of lesions i n the proximal region of the aorta of Lp(a) mice was measured by use o f a computer-assisted image analysis of 20 sections per animal and com pared with that of nontransgenic mice as well as mice expressing eithe r the apo(a) or h-apoB transgene. The control (n = 23) and apo(a) (n = 22) transgenic mice had very small mean lesion areas (607 versus 128 mu m(2) per section). The h-apoB-expressing mice (n = 20) had signific antly higher mean lesion areas (3288 mu m(2) per section) than either the control or apo(a) transgenic animals. Coexpression of apo(a) and h -apoB transgenes resulted in only a modest increase in lesion area (46 78 mu m(2) per section, n = 19). Thus, the expression of human apo(a) in C57BL/6/SJL hybrid mice fed an atherogenic diet failed to significa ntly potentiate the development of aortic fatty lesions in the absence or presence of high levels of h-apoB.