Functional LCAT is not required for macrophage cholesterol efflux to human serum

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• 作者：Laura Calabresi ; Elda Favari ; Elsa Moleri ; Maria Pia Adorni ; Matteo Pedrelli ; Sara Costa ; Wendy Jessup ; Ingrid C. Gelissen ; Petri T. Kovanen ; Franco Bernini ; Guido Franceschini
• 关键词：Familial LCAT deficiency ; High density lipoproteins ; Cholesterol efflux ; Macrophages ; ABCA1
• 刊名：Atherosclerosis
• 出版年：2009
• 出版时间：May 2009
• 年：2009
• 卷：204
• 期：1
• 页码：141-146
• 全文大小：316 K

文摘

Objectives

To evaluate the capacity of serum from carriers of LCAT gene mutations to promote cell cholesterol efflux through the ABCA1, ABCG1, and SR-BI pathways.

Methods

Serum was obtained from 41 carriers of mutant LCAT alleles (14 carriers of two mutant LCAT alleles and 27 heterozygotes) and 10 non-carrier relatives (controls). The capacity of serum to promote cholesterol efflux was tested in pathway-specific cell models.

Results

LCAT deficient sera were significantly more efficient than control sera in promoting cell cholesterol efflux via ABCA1 (3.1 ± 0.3 % for carriers of two mutant LCAT alleles and 2.6 ± 0.2 % for heterozygotes vs. 1.5 ± 0.4 % for controls), and less efficient in promoting ABCG1- and SR-BI-mediated cholesterol efflux. The enhanced capacity of LCAT deficient serum for ABCA1 efflux is explained by the increased content of preβ-HDL, as indicated by the significant positive correlation between ABCA1 efflux and serum preβ-HDL content (R = 0.468, P < 0.001). Moreover, chymase treatment of LCAT deficient serum selectively degraded preβ-HDL and completely abolished ABCA1 efflux. Despite the remarkable reductions in serum HDL levels, LCAT deficient sera were as effective as control sera in removing mass cholesterol from cholesterol-loaded macrophages.

Conclusions

Serum from carriers of LCAT gene mutations has the same capacity of control serum to decrease the cholesterol content of cholesterol-loaded macrophages due to a greater cholesterol efflux capacity via ABCA1.