Mann C J, Yen F T, Grant A M, Bihain B E
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
J Clin Invest. 1991 Dec;88(6):2059-66. doi: 10.1172/JCI115535.
Plasma net cholesteryl ester (CE) transfer and optimum cholesteryl ester transfer protein (CETP) activity were determined in primary hypertriglyceridemic (n = 11) and normolipidemic (n = 15) individuals. The hypertriglyceridemic group demonstrated 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 normolipidemia, but not in hypertriglyceridemia, net CE transfer correlated with VLDL triglyceride (r = 0.92, P less than 0.001). In contrast, net CE transfer in hypertriglyceridemia, but not in normolipidemia, correlated with CETP activity (r = 0.73, P less than 0.01). Correction of hypertriglyceridemia with bezafibrate reduced net CE transfer towards normal and restored the correlation with VLDL triglyceride (r = 0.90, P less than 0.005) while suppressing the correlation with CETP activity. That net CE transfer depends on VLDL concentration was confirmed by an increase of net 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.
在原发性高甘油三酯血症患者（n = 11）和血脂正常者（n = 15）中测定了血浆净胆固醇酯（CE）转运和最佳胆固醇酯转运蛋白（CETP）活性。高甘油三酯血症组的净CE转运增加了两倍，导致VLDL中CE的积累增加。这种净转运增加并未伴随CETP活性的改变。在血脂正常时，而非高甘油三酯血症时，净CE转运与VLDL甘油三酯相关（r = 0.92，P<0.001）。相反，在高甘油三酯血症时，而非血脂正常时，净CE转运与CETP活性相关（r = 0.73，P<0.01）。用苯扎贝特纠正高甘油三酯血症可使净CE转运恢复正常，并恢复与VLDL甘油三酯的相关性（r = 0.90，P<0.005），同时抑制与CETP活性的相关性。通过向血脂正常的血浆中补充纯化的VLDL可使净CE转运增加，从而证实净CE转运取决于VLDL浓度。向血脂正常的血浆中补充纯化的CETP不会刺激净CE转运。相反，向补充了VLDL的血浆和高甘油三酯血症血浆中添加CETP均可增强净CE转运。因此，在正常受试者中，VLDL浓度决定了净CE转运的速率。随着VLDL浓度增加，即高甘油三酯血症时，CETP成为限速因素。
