INFLUENCE OF MOUSE APOLIPOPROTEIN-A-II ON PLASMA-LIPOPROTEINS IN TRANSGENIC MICE

The role of apolipoprotein A-II (apoA-II) in the metabolism of high de nsity lipoproteins (HDL) is poorly understood. Previous studies of nat urally occurring variations of apoA-II in mice have, however, suggeste d that apoA-II expression influences HDL size and concentration. We no w provide definitive evidence of this using transgenic mice overexpres sing mouse apoA-II. Thus, as compared with nontransgenic littermates, transgenic mice possessing 4-fold elevations of apoA-II mRNA and 2-3-f old elevations in plasma apoA-II levels exhibited more than a 2-fold i ncrease in HDL levels as well as about a 25% increase in average HDL d iameter. Overexpression of mouse apoA-II also resulted in a substantia l decrease in the levels of apolipoprotein E associated with HDL, sugg esting that apoA-II can displace apoE from HDL. The apoA-II transgenic mice also exhibited a 2-4-fold increase in plasma very low density an d low density lipoprotein-cholesterol levels, suggesting novel interac tions among the classes of plasma lipoproteins.