ELEVATED HIGH-DENSITY-LIPOPROTEIN CONCENTRATIONS IN HEART-TRANSPLANT RECIPIENTS ARE RELATED TO IMPAIRED PLASMA CHOLESTERYL ESTER TRANSFER AND HEPATIC LIPASE ACTIVITY

Accelerated atherosclerosis is a major complication of heart transplan tation, and is frequently associated with a dyslipoproteinemia charact erized by a paradoxical increase in HDL-cholesterol concentration. To define this abnormality, the lipoprotein profiles of 25 heart transpla nt recipients (HTR) were analyzed and compared with those of 26 contro l subjects. HDL, as separated on the basis of density in 3 subfraction s, were increased in concentration: HDL2: +51%, HDL3a: +29%, HDL3b: +3 2%. HDL2 and HDL3a displayed an enrichment in surface components, phos pholipids, unesterified cholesterol and apo E, leading to an increased size compared with subfractions of similar density in the controls. T he major steps of plasma HDL metabolism were investigated: cholesterol esterification (LCAT activity), cholesteryl ester transfer to apo B-c ontaining lipoproteins (CETP) and the hepatic hydrolysis of HDL compon ents (HL activity). We demonstrated a partial deficiency in CETP (-28% ) and hepatic lipase (-36%) activities with normal LCAT activity. Corr elations in total study population (HTR plus controls) evidenced negat ive associations between CETP activity and HDL3a concentrations and be tween HL activity and HDL2-cholesterol as a percent of total HDL-chole sterol. Therapeutic agents used in post transplantation treatment such as glucocorticoids and/or cyclosporine may be speculated thus to affe ct both CETP and HL activities and, by arresting the HDL cycle in a CE -saturated state, to decrease the efficiency of reverse cholesterol ex traction at the site of the graft.