出版社：American Society for Biochemistry and Molecular Biology
摘要：Reduction of plasma LCAT activity has been observed in severalconditions in which the size of HDL particles is increased;however, the mechanism of this reduction remains elusive. Weinvestigated the plasma activity, mass, and in vivo catabolismof LCAT and its association with HDL particles in human apolipoproteinA-I transgenic, scavenger receptor class B type I knockout (hA-ITg SR-BI–/–) mice. Compared with hA-I Tg mice, hA-ITg SR-BI–/– mice had a 4-fold higher total plasmacholesterol concentration, which occurred predominantly in 13–18nm diameter HDL particles, a significant reduction in plasmaesterified cholesterol-total cholesterol (EC/TC) ratio, andsignificantly lower plasma LCAT activity, suggesting a decreasein LCAT protein. However, LCAT protein in plasma, hepatic mRNAfor LCAT, and in vivo turnover of 35S-radiolabeled LCAT weresimilar in both genotypes of mice. HDL from hA-I Tg SR-BI–/–mice was enriched in sphingomyelin (SM), relative to phosphatidylcholine,and had less associated [35S]LCAT radiolabel and endogenousLCAT activity compared with HDL from hA-I Tg mice. We concludethat the decreased EC/TC ratio in the plasma of hA-ITgSR-BI–/–mice is attributed to a reduction in LCAT reactivity with SM-enrichedHDL particles.Abbreviations: apoE, apolipoprotein E; CE, cholesteryl ester; CETP, cholesteryl ester transfer protein; EC, esterified cholesterol; FC, free cholesterol; FPLC, fast-protein liquid chromatography; hA-ITg, human apolipoprotein A-I transgenic; hrLCAT, human recombinant lecithin:cholesterol acyltransferase; PC, phosphatidylcholine; PLTP, phospholipid transfer protein; rHDL, recombinant high density lipoprotein; SM, sphingomyelin; SR-BI, scavenger receptor class B type I; TC, total cholesterol
Supplementary key words high density lipoproteins • cholesterol • sphingomyelin • lecithin:cholesterol acyltransferase • scavenger receptor class B type I
