Plasma kinetics of a cholesterol-rich microemulsion in patients submitted to heart transplantation.

BACKGROUND: Development of coronary graft disease is currently the main cause of late heart-transplantation (HT) failure. HT patients frequently show hypercholesterolemia as well as alterations in chylomicron metabolism. These postHT changes may be important in coronary graft disease development. To clarify whether hypercholesterolemia is caused by decreased low-density lipoprotein (LDL) removal from the plasma, we studied the plasma kinetics of a cholesterol-rich emulsion that binds to LDL receptor. METHODS: We studied 13 HT patients and 13 healthy normolipidemic subjects paired for sex, age, and body mass index. An emulsion labeled with C-cholesteryl oleate was injected intravenously, and blood samples were collected in predetermined intervals (5 minutes, 1, 2, 4, 6, and 8 hours) to determine the radioactivity decay curves and to calculate the fractional clearance rates (FCR). RESULTS: The plasma level of total cholesterol, LDL cholesterol, high-density lipoprotein cholesterol, and apo B were greater in HT group than in the control group (P<0.005). FCR C-cholesteryl oleate was smaller in HT patients when compared with the control group (P=0.02). CONCLUSION: The results showed that HT patients have a deficiency in the mechanisms of LDL removal from the plasma, as tested by the cholesterol-rich emulsion, and this may be important in the development of coronary graft disease.

In vitro simultaneous transfer of lipids to HDL in coronary artery disease and in statin treatment.

The exchange of lipids with cells and other lipoproteins is a crucial process in HDL metabolism and for HDL antiatherogenic function. Here, we tested a practical method to quantify the simultaneous transfer to HDL of phospholipids, free-cholesterol, esterified cholesterol and triacylglycerols and to verify the lipid transfer in patients with coronary artery disease (CAD) or undergoing statin treatment. Twenty-eight control subjects without CAD, 27 with CAD and 25 CAD patients under simvastatin treatment were studied. Plasma samples were incubated with a donor nanoemulsion prepared by ultrasonication of the constituent lipids and labeled with radioactive lipids; % lipids transferred to HDL were quantified in the HDL-containing supernatant after chemical precipitation of non-HDL fractions and the nanoemulsion. The assay was precise and reproducible. Increase of temperature (4-37 degrees C), of incubation period (5 min to 2 h), of HDL-cholesterol concentration (33-244 mg/dL) and of mass of nanoemulsion lipids (0.075-0.3 mg/microL) resulted in increased lipid transfer from the nanoemulsion to HDL. In contrast, increasing pH (6.5-8.5) and albumin concentration (3.5-7.0 g/dL) did not affect lipid transfer. There was no difference between CAD and control non-CAD with regard to the lipid transfer, but statin treatment reduced the transfer to HDL of all four lipids. The test herein described is a valid and practical tool for exploring an important aspect of HDL metabolism.