TRANSGENIC MICE EXPRESSING HUMAN PHOSPHOLIPID TRANSFER PROTEIN HAVE INCREASED HDL NON-HDL CHOLESTEROL RATIO

The role of plasma phospholipid transfer protein (PLTP) in lipoprotein metabolism is poorly understood. In vitro studies suggest that PLTP i nfluences HDL size and composition and transfers phospholipids among l ipoproteins. To provide an in vivo model for studies of PLTP physiolog y, transgenic mice that express human PLTP were generated. Human PLTP transcripts were detected in total RNA from adipose tissue, lung, hear t, and spleen of the two distinct lines (A and C) of transgenic mice. Despite minimal expression of human PLTP in the liver of these transge nic mice and similar plasma phospholipid transfer activity in transgen ic and non-transgenic mice (19.1 +/- 3.1 vs 18.9 +/- 2.7 mu mol/ml/h), differences in lipoprotein levels were observed between transgenic an d control mice receiving the same chow diet. Male transgenic mice of l ine C had significantly higher HDL cholesterol than control mice (76.4 +/- 4.6 vs 71.9 +/- 7.0 mg/dl, p<0.05) and the male transgenic mice o f lines A and C had a significantly lower non-HDL cholesterol (15.1 +/ - 4.1 and 15.6 +/- 4.7 vs 20.9 +/- 5.5 mg/dl, P<0.01 and P<0.02) and a significantly higher HDL cholesterol/non-HDL cholesterol ratio than t he control mice (5.3 +/- 1.3 and 5.5 +/- 2.2 vs 3.9 +/- 1.9 mg/dl, P<0 .01 and P<0.02). Female mice from transgenic line C had higher HDL cho lesterol than control mice (64.6 +/- 4.8 vs 57.4 +/- 5.1 mg/dl, P<0.01 ) while female mice from line A tended to have higher HDL cholesterol/ non-HDL cholesterol ratio than control mice (5.5 +/- 3.7 vs 3.8 +/- 1 .4). These observations suggest that expression of PLTP in peripheral tissues play an important role in lipoprotein metabolism. Expression o f human PLTP produced a more favorable lipoprotein profile and thus, e nhanced expression of PLTP could potentially retard atherosclerosis.