High-density lipoprotein and the dynamics of atherosclerotic lesions.

Plump et al 1 reported in 1994 that the expression of a human transgene for apoA-I, the major apolipoprotein of HDL, in apoE knockout mice dramatically reduced lesion formation. In the present issue of Circulation, Rong et al2 demonstrate that the composition and structure of advanced atherosclerotic plaques can be significantly altered by the expression of this same transgene. Rong and colleagues2 used a novel transplant model. They fed apoE knockout mice a Western diet for 6 months to generate advanced lesions. Subsequently, they surgically removed portions of the aorta from these mice and transplanted them into the aortas of syngeneic mice on a chow diet, some of which also expressed the transgene for human apoA-I. The recipient mice expressing the human transgene had 2.5-fold higher HDL cholesterol levels and expressed 130 15 mg/dL of human apoA-I. The non-HDL cholesterol levels were approximately half of those that had been present in the donor mice and were similar, regardless of whether the transgene was expressed or not. Five months later, despite non-HDL cholesterol levels that were half those of the donor mice, there was progression in the transplanted lesions, although there was less progression in the mice expressing the human apoA-I transgene. However, the characteristics of the lesions were dramatically different. The recipients expressing the transgene had a 80% decrease in lesion macrophage area and a 300% increase in smooth muscle cell content, with most of the changes occurring in the superficial subendothelial layer.