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 pre-HDL, as indicated by the significant positive correlation between ABCA1 efflux and serum pre-HDL content (R = 0.468, P < 0.001). Moreover, chymase treatment of LCAT deficient serum selectively degraded pre-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.

Functional LCAT is not required for macrophage cholesterol efflux to human serum / Calabresi, L.; Favari, Elda; Moleri, E.; Adorni, Maria Pia; Pedrelli, M.; Costa, S.; Jessup, W.; Gelissen, I. C.; Kovanen, P. T.; Bernini, Franco; Franceschini, G.. - In: ATHEROSCLEROSIS. - ISSN 0021-9150. - 204 (1):(2009), pp. 141-146. [10.1016/j.atherosclerosis.2008.08.038]

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

FAVARI, Elda;ADORNI, Maria Pia;BERNINI, Franco;
2009-01-01

Abstract

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 pre-HDL, as indicated by the significant positive correlation between ABCA1 efflux and serum pre-HDL content (R = 0.468, P < 0.001). Moreover, chymase treatment of LCAT deficient serum selectively degraded pre-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.
2009
Functional LCAT is not required for macrophage cholesterol efflux to human serum / Calabresi, L.; Favari, Elda; Moleri, E.; Adorni, Maria Pia; Pedrelli, M.; Costa, S.; Jessup, W.; Gelissen, I. C.; Kovanen, P. T.; Bernini, Franco; Franceschini, G.. - In: ATHEROSCLEROSIS. - ISSN 0021-9150. - 204 (1):(2009), pp. 141-146. [10.1016/j.atherosclerosis.2008.08.038]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2293416
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