Cellular cholesterol efflux and cholesterol loading capacity of serum: effects of LDL-apheresis

Adorni, Maria Pia; Zimetti, Francesca; Puntoni, M.; Bigazzi, Federico; Sbrana, Francesco; Minichilli, Fabrizio; Ronda, Nicoletta; Favari, Elda; Sampietro, Tiziana

doi:10.1194/jlr.p024810

Cited by 39 publications

(39 citation statements)

References 28 publications

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“…Cholesterol loading capacity (CLC) was measured as previously described 15 and defined as macrophage cholesterol content after exposure of cells to serum and expressed as µg cholesterol / mg protein.…”

Section: Cholesterol Loading Capacitymentioning

confidence: 99%

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Lomitapide affects HDL composition and function

et al. 2016

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Section: Cholesterol Loading Capacitymentioning

confidence: 99%

“…The apoB-depleted serum CEC specific for the three cholesterol efflux pathways (ABCA1, ABCG1, SR-BI) was evaluated in established cell culture models, as previously described 17,18 . Cellular cholesterol content before and after serum exposure was measured fluorimetrically as previously described 15 .…”

Section: Cholesterol Loading Capacitymentioning

confidence: 99%

Lomitapide affects HDL composition and function

et al. 2016

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“…A pool of human sera as reference standard 1 (St1) was tested in each assay, and its effl ux capacity was used to normalize the patient sample values from different experiments to correct for the interassay variability. A second pool of human sera as reference standard 2 (St2) was tested in each assay, and its effl ux capacity, after normalization, was the index of the intra-assay variability ( 32 ). Calculated mean intra-and interassay coeffi cients of variation were 5.95% and 9.53%, respectively.…”

Section: Cecmentioning

confidence: 99%

“…Stimulation of J774 murine macrophages with cAMP (0.3 mM) for 18 h up-regulates the ABCA1 protein ( 30,31 ). In such conditions, total release of cholesterol occurs mainly by ABCA1 and aqueous diffusion ( 4,32 ). ABCA1-mediated CEC was calculated as the difference in effl ux between ABCA1 expressing J774 and J774 in basal conditions ( 33 ).…”

Section: Cecmentioning

confidence: 99%

“…cAMPinduced ABCA1 expression was verifi ed by the increase in effl ux to 10 g/ml apoA-I used as ABCA1 specifi c extracellular acceptor ( 31,32 ). A pool of human sera as reference standard 1 (St1) was tested in each assay, and its effl ux capacity was used to normalize the patient sample values from different experiments to correct for the interassay variability.…”

Section: Cecmentioning

confidence: 99%

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ABCA1-dependent serum cholesterol efflux capacity inversely correlates with pulse wave velocity in healthy subjects

Favari

Ronda

Adorni

et al. 2013

Journal of Lipid Research

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Newly Identified Antiatherosclerotic Activity of Methotrexate and Adalimumab: Complementary Effects on Lipoprotein Function and Macrophage Cholesterol Metabolism

Ronda

Greco

Adorni

et al. 2015

Arthritis & Rheumatology

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Objective Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis. The reduction in cardiovascular risk that is induced by methotrexate (MTX) and anti–tumor necrosis factor α agents in RA is considered secondary to their anti‐inflammatory action, but their effects on serum lipoprotein function and foam cell formation are unknown. The reduced capacity of high‐density lipoprotein (HDL) to promote cell cholesterol efflux and the increased serum cell cholesterol‐loading capacity (CLC) demonstrated in RA may contribute to foam cell development. The aim of this study was to investigate the influence of MTX and adalimumab treatment on serum cholesterol efflux capacity (CEC) and CLC in RA patients and to study the in vitro effects of the two drugs on macrophage cholesterol handling. Methods Sera from RA patients treated with MTX (n = 34) or with adalimumab and MTX (n = 22) obtained before treatment, after 6 weeks of treatment, and after 6 months of treatment were analyzed for CEC and CLC by radioisotopic and fluorometric techniques, respectively. The influence of MTX and adalimumab on macrophage cholesterol efflux and uptake was evaluated in vitro using human THP‐1–derived macrophages. Results MTX treatment was associated with increases in serum HDL, low‐density lipoprotein, and total cholesterol levels and with ATP‐binding cassette G1–mediated and scavenger receptor class B type I (SR‐BI)–mediated increases in CEC; MTX treatment was not associated with modifications in CLC. Adalimumab treatment was associated with increases in serum HDL levels, a transient increase in SR‐BI–mediated CEC, a transient decrease in ATP‐binding cassette A1–mediated CEC, and a significant reduction in CLC; in addition, adalimumab reduced macrophage cholesterol uptake in vitro. Conclusion Antiatherosclerotic activity asso‐ciated with MTX and adalimumab may be mediated by beneficial and complementary effects on lipoprotein functions and on macrophage cholesterol handling. As a whole, these mechanisms may oppose foam cell formation.

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Cellular cholesterol efflux and cholesterol loading capacity of serum: effects of LDL-apheresis

Cited by 39 publications

References 28 publications

Lomitapide affects HDL composition and function

Lomitapide affects HDL composition and function

ABCA1-dependent serum cholesterol efflux capacity inversely correlates with pulse wave velocity in healthy subjects

Newly Identified Antiatherosclerotic Activity of Methotrexate and Adalimumab: Complementary Effects on Lipoprotein Function and Macrophage Cholesterol Metabolism

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