Platelet function in patients with familial hypertriglyceridemia: Evidencethat platelet reactivity is modulated by apolipoprotein E content of very-low-density lipoprotein particles

We evaluated platelet function in patients with familial hypertriglyceridem ia (FHTG). Compared with healthy gender-matched controls, platelets from pa tients showed lower aggregation (P < .01) and thromboxane formation (P < .0 1) in response to collagen. Very-low-density lipoprotein (VLDL) particles o btained from the patients inhibited collagen induced aggregation, whereas V LDL particles from controls had opposite effects. The VLDL-induced effect w as regulated by its apolipoprotein E (apoE) content. indeed, apoE-VLDL-rich fractions caused antiaggregative effects, whereas apoE VLDL-poor fractions produced a strong proaggregative response. Since we have recently demonstr ated that VLDL particles may regulate the activity of platelet low-density lipoprotein (LDL) receptor by a phenomenon of downregulation and desensitiz ation, in this study, we have investigated the effect of prolonged exposure to circulating VLDL levels on the activity of platelet LDL receptor by a d ouble-blind controlled study with gemfibrozil (600 mg twice daily) in 18 su bjects with FHTG. Platelets from patients exhibited fewer platelet LDL rece ptors and I-125-LDL binding was saturable at a lower protein concentration. After 6 months, gemfibrozil therapy versus placebo had a marked lipid-lowe ring effect significantly decreased triglycerides (61%), VLDL cholesterol ( 72%), apoB (28%), and apoE (55%), and increased high-density lipoprotein (4 4%) and apoA-1(18%). Furthermore, gemfibrozil affected the apoprotein compo sition of VLDL: total protein increased by 28%, the molar ratio of apoE to apoB decreased 64%, and apoE content decreased 55%. However, no differences in phospholipid, triglyceride, or total cholesterol were detected. Moreove r, platelet function was markedly altered by gemfibrozil therapy. Collagen induced aggregation and thromboxane formation were significantly enhanced ( P < .01). The initial antiaggregative pattern of VLDL particles was changed to a significant proaggregative effect (P < .01), and the number of LDL bi nding sites was markedly upregulated (P < .001). Both receptor upregulation and the change in the aggregative effect of VLDL particles were associated with the reduction of apoE content in VLDL particles (P < .05). The overal l results indicate that in the regulation of platelet reactivity in hypertr iglyceridemic patients, apoE content of VLDL particles and their interactio n with the platelet LDL receptor are involved. Copyright (C) 2000 by W.B. S aunders Company.