Genetics, metabolism and atherogenicity of LP(A)

Lipoprotein(a) [Lp(a)J is composed of a panicle of low density lipoprotein (LDL) to which is attached a large, highly polymorphic glycoprotein called apolipoprotein(a) [apo(a)]. In humans high plasma levels of Lp(a) are associated with an increased risk of atherosclerosis Plasma levels of Lp(a) vary over a 1000-fold range and are largely determined by sequence differences in the apo(a) gene. Most species do not express Lp(a), which has limited our ability to probe the mechanistic link between Lp(a) and atherosclerosis To produce an animal model in which to study the metabolism and the atherogenic effects of Lp(a), transgenic mice expressing the both the human apo(a) and apoB-IOO genes were developed Using these animals, inconsistent results have been reported by different laboratories regarding the association between apo(a) or Lp(a) and atherosclerosis This lecture will focus on recent insights into the metabolism of apo(a), which may provide clues as to source for the variable expression of atherosclerosis in these transgenic mice.