Mechanism of plasma cholesteryl ester transfer in hypertriglyceridemia.

Plasma net cholesteryl ester (CE) transfer and optimum cho- lesteryl ester transfer protein (CETP) activity were determined in primary hypertriglyceridemic (a = 11) and normolipidemic (a = 15) individuals. The hypertriglyceridemic group demon- strated threefold greater net CE transfer leading to enhanced accumulation of CE in VLDL. This increased net transfer was not accompanied by a change in CETP activity. In normolipide- mia, but not in hypertriglyceridemia, net CE transfer correlated with VLDL triglyceride (r = 0.92, P < 0.001). In contrast, net CE transfer in hypertriglyceridemia, but not in normolipide- mia, correlated with CETP activity (r = 0.73, P < 0.01). Correc- tion of hypertriglyceridemia with bezafibrate reduced net CE transfer towards normal and restored the correlation with VLDL triglyceride (r = 0.90, P < 0.005) while suppressing the correlation with CETP activity. That net CE transfer depends on VLDL concentration was confirmed by an increase ofnet CE transfer in normolipidemic plasma supplemented with purified VLDL. Supplementation of purified CETP to normolipidemic plasma did not stimulate net CE transfer. In contrast, net CE transfer was enhanced by addition of CETP to both plasma supplemented with VLDL and hypertriglyceridemic plasma. Thus, in normal subjects, VLDL concentration determines the rate of net CE transfer. CETP becomes rate limiting as VLDL concentration increases, i.e, in hypertriglyceridemia. (J. Clin. Invest. 1991. 88:2059-2066.) Key words: cholesteryl ester transfer protein * very low density lipoprotein -high density lipoprotein -cardiovascular disease * reverse cholesterol trans- port MO. Bezafibrate (2-[4-[2-[(4-chlorobenzoyl)amino]-ethyl]phenoxy]-2methylpropanoic acid) was obtained from Boehringer Mannheim (for- merly MCP Pharmaceuticals), Livingstone, Scotland.