HUMAN APOLIPOPROTEIN-A-I PREVENTS ATHEROSCLEROSIS ASSOCIATED WITH APOLIPOPROTEIN[A] IN TRANSGENIC MICE

Elevated levels of apolipoprotein[a] (apo[a]) and apolipoprotein A-I ( apoA-I) are associated, respectively, with increased and decreased ath erosclerosis risk, in both humans and transgenic mice. To investigate the interactions of these two important lipid-associated proteins, we assessed the effect of expression of human apoA-I and apo[a] transgene s, both singularly and together, on murine atherogenesis, Mice express ing the apo[a] transgene have a lipoprotein profile similar to nontran sgenic controls, yet have significantly increased susceptibility to di et-induced atherosclerosis. Compared to mice expressing only the apo[a ] transgene, mice expressing both apo[a] and apoA-I transgenes have tw ofold greater high density lipoprotein (HDL) concentrations and approx imately a 20-fold decrease in development of early atherosclerotic les ions. The finding of decreased atherosclerosis in the setting of eleva ted apo[a] and apoA-I suggests that elevations of apoA-I and HDL have a dominant effect in reducing atherosclerosis susceptibility in variou s settings, including those not associated with alterations of plasma lipids.