Lecithin Cholesterol Acyltransferase: An Anti- or Pro-atherogenic Factor?

Rousset, Xavier; Shamburek, Robert D.; Vaisman, Boris; Amar, Marcelo; Remaley, Alan T.

doi:10.1007/s11883-011-0171-6

Cited by 91 publications

(95 citation statements)

References 46 publications

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“…Alternatively, the increased FC content of lipoproteins and the redistribution of LPL-modulating proteins such as apoC-II and apoC-III, which have been described to occur in familial LCAT defi ciency ( 7,8 ), could also account for the decreased lipolysis and clearance of apoB-containing lipoproteins. The results from this study are also consistent with previous animal models of either increased or decreased LCAT expression, which have shown that the effect of LCAT on the level of pro-atherogenic apoB-containing particles is the best predictor of whether LCAT promotes or decreases atherosclerosis in a given animal model ( 7,8 ).…”

Section: Discussionmentioning

confidence: 99%

Increased plasma cholesterol esterification by LCAT reduces diet-induced atherosclerosis in SR-BI knockout mice

Thacker

Rousset

Esmail

et al. 2015

Journal of Lipid Research

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Section: Discussionmentioning

confidence: 99%

Increased plasma cholesterol esterification by LCAT reduces diet-induced atherosclerosis in SR-BI knockout mice

Thacker

Rousset

Esmail

et al. 2015

Journal of Lipid Research

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“…Investigations in various animal models overexpressing or lacking LCAT provided inconsistent results (recently reviewed in Ref. 7 ). LCAT overexpression in mice or rabbits remarkably increased plasma HDL levels and was associated with protection against diet-induced atherosclerosis in rabbits but not in mice.…”

Section: Statistical Analysesmentioning

confidence: 99%

Plasma lecithin:cholesterol acyltransferase and carotid intima-media thickness in European individuals at high cardiovascular risk

Calabresi

Baldassarre

Simonelli

et al. 2011

Journal of Lipid Research

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The lecithin:cholesterol acyltransferase (LCAT) enzyme catalyzes the transacylation of the sn-2 fatty acid of lecithin to the free 3-OH group of cholesterol, generating cholesteryl ester (CE) and lysolecithin ( 1 ). In this way, the LCAT Abstract Lecithin:cholesterol acyltransferase (LCAT) is the enzyme responsible for cholesterol esterifi cation in plasma. LCAT is a major factor in HDL remodeling and metabolism, and it has long been believed to play a critical role in macrophage reverse cholesterol transport (RCT). The effect of LCAT on human atherogenesis is still controversial. In the present study, the plasma LCAT concentration was measured in all subjects (n = 540) not on drug treatment at the time of enrollment in the multicenter, longitudinal, observational IMPROVE study. Mean and maximum intimamedia thickness (IMT) of the whole carotid tree was measured by B-mode ultrasonography in all subjects. In the entire cohort, LCAT quartiles were not associated with carotid mean and maximum IMT ( P for trend 0.95 and 0.18, respectively), also after adjustment for age, gender, HDLcholesterol (HDL-C), and triglycerides. No association between carotid IMT and LCAT quartiles was observed in men ( P =0.30 and P =0.99 for mean and maximum IMT, respectively), whereas carotid IMT increased with LCAT quartiles in women ( P for trend 0.14 and 0.019 for mean and maxi-

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“…By contrast, apoE-and apoA-I-containing lipoprotein particles in CSF are 11-20 nm spherical particles containing 70% of their cholesterol in the esterifi ed form, with a similar density to ␣ -HDL found in plasma ( 38,(40)(41)(42). Plasma HDL maturation is catalyzed by LCAT, which esterifi es free cholesterol (FC) to cholesteryl ester (CE) to form the lipid core critical for conversion of discoidal pre ␤ -HDL to mature spherical ␣ -HDL ( 43 ). In addition to HDL, LCAT can also esterify FC contained on other lipoprotein particles, thus infl uencing their metabolism as well.…”

Section: Csf Plasma and Tissue Collectionmentioning

confidence: 99%

“…In addition to HDL, LCAT can also esterify FC contained on other lipoprotein particles, thus infl uencing their metabolism as well. In plasma, HDL maturation maintains the gradient of FC between the cell membrane and HDL surface, thereby driving cholesterol effl ux, a key process in reverse cholesterol transport ( 43 ). containing complete protease inhibitor (Roche Applied Science) in a Tissuemite homogenizer for 20 s, sonicated at 20% output for 10 s, and clarifi ed by centrifugation at 16,600 rcf for 45 min at 4°C.…”

Section: Csf Plasma and Tissue Collectionmentioning

confidence: 99%

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LCAT deficiency does not impair amyloid metabolism in APP/PS1 mice

Stukas

Freeman

Lee

et al. 2014

Journal of Lipid Research

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Journal of Lipid Research Volume 55, 20141721 of the apoE4 allele increases risk and decreases the age of onset of late-onset AD ( 2 ), the putative roles of apoE in AD pathogenesis have been a topic of intensive focus. apoE is the primary apolipoprotein secreted by astrocytes and microglia in the CNS, and lipidation of nascent apoEcontaining discoidal particles eventually leads to the formation of mature CNS HDL-like particles in cerebrospinal fl uid (CSF) ( 1, 3 ). It is well-established that amyloid burden in humans follows an isoform-dependent pattern of apoE4>apoE3>apoE2 ( 4-6 ). In contrast to human apoE, murine apoE exists in only one isoform with limited homology to human apoE. Amyloid burden is robust in AD mice expressing murine apoE and nearly abrogated in apoE-defi cient mice ( 7-11 ). Reconstitution of human apoE isoforms into AD mice greatly delays amyloid deposition relative to murine apoE, but retains the human isoform-specifi c infl uence on amyloid accumulation (12)(13)(14)(15)(16)(17). Taken together, the relative amyloid burden across murine and human apoE is: murine apoE>>apoE4>apoE3>apoE2>>apoE Ϫ / Ϫ . These observations clearly show that apoE affects amyloid burden in vivo. In vivo, neither apoE isoform nor gene dose significantly affects the rate of ␤ -amyloid (A ␤ ) production from amyloid precursor protein ( 16,17 ), leading to the consensus that apoE is largely involved in modulating the clearance of A ␤ peptides from the brain. apoE participates in each of the three known pathways of A ␤ clearance, including proteolytic degradation, egress across the blood-brain barrier, and interstitial fl uid drainage, although many details remain poorly understood ( 18,19 ). It is important to note, however, that apoE isoforms, levels, and lipidation status are all important variables.Abstract A key step in plasma HDL maturation from discoidal to spherical particles is the esterifi cation of cholesterol to cholesteryl ester, which is catalyzed by LCAT. HDL-like lipoproteins in cerebrospinal fl uid (CSF) are also spherical, whereas nascent lipoprotein particles secreted from astrocytes are discoidal, suggesting that LCAT may play a similar role in the CNS. In plasma, apoA-I is the main LCAT activator, while in the CNS, it is believed to be apoE. apoE is directly involved in the pathological progression of Alzheimer's disease, including facilitating ␤ -amyloid (A ␤ ) clearance from the brain, a function that requires its lipidation by ABCA1. However, whether apoE particle maturation by LCAT is also required for A ␤ clearance is unknown. Here we characterized the impact of LCAT defi ciency on CNS lipoprotein metabolism and amyloid pathology. Deletion of LCAT from APP/PS1 mice resulted in a pronounced decrease of apoA-I in plasma that was paralleled by decreased apoA-I levels in CSF and brain tissue, whereas apoE levels were unaffected. Furthermore, LCAT defi ciency did not increase A ␤ or amyloid in APP/PS1 LCAT ؊ / ؊ mice. Finally, LCAT expression and plasma activity were unaffected by age or the ons...

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Lecithin Cholesterol Acyltransferase: An Anti- or Pro-atherogenic Factor?

Cited by 91 publications

References 46 publications

Increased plasma cholesterol esterification by LCAT reduces diet-induced atherosclerosis in SR-BI knockout mice

Increased plasma cholesterol esterification by LCAT reduces diet-induced atherosclerosis in SR-BI knockout mice

Plasma lecithin:cholesterol acyltransferase and carotid intima-media thickness in European individuals at high cardiovascular risk

LCAT deficiency does not impair amyloid metabolism in APP/PS1 mice

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