Intralipid infusion in patients with familial hypercholesterolemia. Effect of serum and plasma lipoproteins on platelet aggregation and on macrophage cholesterol metabolism.
Intralipid infusion into normal volunteers was recently shown to possess anti-atherogenic properties. We studied the effect of intralipid infusion in patients with severe Familial Hypercholesterolemia (FH) refractory to conventional therapy. FH patients and normal subjects, who served as controls, were given an intravenous infusion of intralipid for 6 h. Serum samples taken from both groups before, during and after intralipid infusion were studied for their ability to inhibit cellular cholesterol accumulation by macrophages. A significantly lower rate of cellular cholesterol esterification (of 46%, P less than 0.005 and 44%, P less than 0.005 in patients and normals, respectively) was demonstrated in macrophages incubated with serum obtained during intralipid infusion compared to those incubated with preinfusion serum. The maximal effect was demonstrated with serum samples taken at the end of the infusion, but the inhibitory effect persisted even at 24 h post-infusion. It was found that chylomicron like particles could induce the above-mentioned effects on macrophage cholesterol esterification. A significant decrement of 50% (P less than 0.005) in aggregation of platelets isolated from plasma samples taken during and after intralipid infusion from both groups was demonstrated, when compared to platelets isolated in the preinfusion state. This effect persisted 18 h subsequent to infusion. We conclude that intralipid infusion abolishes serum ability to stimulate cholesterol esterification in cultured macrophages, and exhibits inhibitory effects upon platelet aggregation. If similar events occur in the arterial wall, intralipid might inhibit foam cell formation.
Hayek
T
T
Rambam Medical Center, Technion Faculty of Medicine, Haifa, Israel.
Fuhrman
B
B
Levy
Y
Y
Aviram
M
M
Brook
J G
JG
D000293:Adolescent; D000328:Adult; D002784:Cholesterol / Q000378:metabolism; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy*; D008074:Lipoproteins / Q000097:blood; D008264:Macrophages / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors
D005217:Fat Emulsions, Intravenous; D008074:Lipoproteins; D010975:Platelet Aggregation Inhibitors; D002784:Cholesterol