Relationship of high density lipoprotein composition to plasma lecithin: cholesterol acyltransferase concentration in men

Miller, N. E.; Rajput-Williams, J.; Nanjee, M. Nazeem; Samuel, Leslie; Albers, John J.

doi:10.1016/0021-9150(88)90005-6

Cited by 24 publications

(11 citation statements)

References 32 publications

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“…The absence of an association between plasma LCAT levels and HDL-C was previously described by Albers et al ( 28,29 ) in both normolipidemic and hyperlipidemic volunteers but not in two other small cross-sectional studies in which a positive correlation between LCAT levels, LCAT activity, and HDL-C was found ( 30,31 ). Taken the results of the current larger and prospective analysis, it could be argued We did not observe a correlation between LCAT levels and HDL-C when analyzing men and women separately or when both sexes were combined.…”

Section: Plasma Lcat Levels and Lipid Metabolismmentioning

confidence: 81%

Plasma levels of lecithin:cholesterol acyltransferase and risk offuture coronary artery disease in apparently healthy men and women: aprospective case-control analysis nested in the EPIC-Norfolk populationstudy

Holleboom

Kuivenhoven

Vergeer

et al. 2010

Journal of Lipid Research

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This article is available online at http://www.jlr.org Supplementary key words high-density lipoprotein cholesterol • atherosclerosis • lipoproteins • epidemiology • European Prospective Investigation into Cancer and NutritionLCAT hydrolyzes the sn-2 acyl group of phosphatidylcholine and subsequently transfers and esterifi es the fatty acid to free cholesterol, thereby using apolipoprotein (apo) A-I as cofactor ( 1 ). The reaction products are thus cholesteryl ester (CE) and lysophosphatidylcholine. The vast majority of CE in the blood circulation is generated by this enzymatic reaction. LCAT is primarily active on HDL and as such drives the maturation of small nascent HDL discs to larger spherical HDL ( 2 ). In catalyzing the esterifi cation of free cholesterol, LCAT has been proposed to maintain a concentration gradient of free cholesterol from cells to HDL, thereby facilitating reverse cholesterol transport ( 3, 4 ). LCAT-defi cient patients present with almost complete HDL defi ciency because they are unable to form mature HDL, which in turn leads to a rapid clearance of nascent HDL from the circulation ( 2, 5 ).Based on our current understanding of HDL metabolism, it is not clear whether LCAT is pro-or antiatherogenic ( 6, 7 ): the generation of CE on HDL by LCAT can be regarded as anti-atherogenic since this action increases HDL cholesterol (HDL-C) levels, but in the presence of cholesteryl ester transfer protein (CETP) and triglyceride-rich lipoproteins, the CE will be transferred to apoBAbstract LCAT plays a key role in the maturation of HDL, as evidenced by low HDL-cholesterol levels in carriers of deleterious mutations in LCAT . However, the role of LCAT in atherosclerosis is unclear. We set out to study this in a prospective study. Plasma LCAT levels, which strongly correlate with LCAT activity, were measured in baseline nonfasting samples of 933 apparently healthy men and women who developed coronary artery disease (CAD) and 1,852 matched controls who remained free of CAD during 6 year follow-up. LCAT levels did not differ between cases and controls but were higher in women than men. Stratifi cation into LCAT quartiles revealed a positive association with plasma LDL-cholesterol and triglyceride levels in the unexpected absence of an association with HDL-cholesterol. In mixed-gender analyses, the odds ratio (OR) for future CAD in the highest LCAT quartile versus the lowest was 1.00 [confi dence interval (CI): 0.76-1.29, P for linearity = 0.902], although opposite trends were observed in men and women. In fact, high LCAT levels were associated with an increased CAD risk in women (unadjusted OR 1.45, CI: 0.94-2.22, P for linearity = 0.036). In contrast to our studies in carriers of LCAT mutations, the current data show that low LCAT plasma levels are not associated with increased atherosclerosis in the general population. -Holleboom, A. G., J. A. Kuivenhoven, M. Vergeer, G. K. Hovingh, J. N. van Miert, N. J. Wareham, J. J. P. Kastelein, K-T. Khaw, and S. M. Boekholdt . Plasma levels of lecithin:choleste...

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Section: Plasma Lcat Levels and Lipid Metabolismmentioning

confidence: 81%

Plasma levels of lecithin:cholesterol acyltransferase and risk offuture coronary artery disease in apparently healthy men and women: aprospective case-control analysis nested in the EPIC-Norfolk populationstudy

Holleboom

Kuivenhoven

Vergeer

et al. 2010

Journal of Lipid Research

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“…Based on such considerations Brinton et al (20) used the HDL-C/(ApoA-I + ApoA-II) ratio as a surrogate for HDL size (see derivation in Supplemental Data, section 4). Similarly Miller (24, 25) used the HDL-C/ApoA-I ratio and noted its connection to the distribution of HDL2 and HDL3 particles; while Fournier reported a strong inverse relationship between triglyceride levels and the HDL-C/ApoA-I ratio (26). Most recently Kimak (27) reported a lower HDL-C/ApoA-I ratio in post-renal transplant patients indicative of smaller particles.…”

Section: Discussionmentioning

confidence: 99%

A Comparison of the Theoretical Relationship between HDL Size and the Ratio of HDL Cholesterol to Apolipoprotein A-I with Experimental Results from the Women's Health Study

Mazer¹,

Giulianini

Paynter

et al. 2013

Clinical Chemistry

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Background HDL size and composition vary among individuals and may be associated with cardiovascular disease and diabetes. We investigated the theoretical relationship between HDL size and composition using an updated version of the spherical model of lipoprotein structure proposed by Shen et al. and compared its predictions with experimental data from the Women’s Health Study (WHS). Methods The Shen model was updated to predict the relationship between HDL diameter and the ratio of HDL-cholesterol (HDL-C) to apolipoprotein A-I (ApoA-I) plasma concentrations, i.e., the HDL-C/ApoA-I ratio. In WHS (n=26,772), NMR spectroscopy was used to measure the average HDL diameter (davg,NMR) and particle concentration (HDL-P); HDL-C and ApoA-I (mg/dL) were measured by standardized assays. Results The updated Shen model predicts a quasi-linear increase of HDL diameter with the HDL-C/ApoA-I ratio, consistent with the measured davg,NMR values from WHS, which ranged between 8.0 and 10.8 nm and correlated positively with the HDL-C/ApoA-I ratio (r=0.608, p<2.2×10−16). The WHS data were further described by a linear regression equation: dWHS (nm) = 4.66 + 12.31 HDL-C/ApoA-I. The validity of this equation for estimating HDL size was assessed with data from CETP deficiency and pharmacologic inhibition. We also illustrate how HDL-P can be estimated from the HDL size and ApoA-I level. Conclusions This study provides a large-scale experimental examination of the updated Shen model, offers new insights into HDL structure, composition and remodeling, and suggests that the HDL-C/ApoA-I ratio could be a readily available biomarker for estimating HDL size and HDL-P.

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“…31 Smaller HDL 3 molecules are the best inducers to esterification and thus LCAT activity. 32 LCAT levels positively associate with plasma LDL-C, TG levels, and cardiovascular risk. 33 Therefore, LCAT may contribute to HDL function, particularly among subjects with low HDL-C. Our observations support previous cross-sectional studies in which the authors indicated that HDL 3 rather than HDL 2 is related positively to the LCAT concentration.…”

Section: Discussionmentioning

confidence: 96%

“…33 Therefore, LCAT may contribute to HDL function, particularly among subjects with low HDL-C. Our observations support previous cross-sectional studies in which the authors indicated that HDL 3 rather than HDL 2 is related positively to the LCAT concentration. 32,33 Hence, LCAT is more functional in low HDL-C mileu; this suggests that the increase of LCAT enzyme level is compensatory in the settting of increasing TG and TC levels.…”

Section: Discussionmentioning

confidence: 97%

Effects of lecithin: Cholesterol acyltransferase genotypes, enzyme levels, and activity on high-density lipoprotein levels

Ağırbaşlı

Çirakoğlu

Eren

et al. 2011

Journal of Clinical Lipidology

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Relationship of high density lipoprotein composition to plasma lecithin: cholesterol acyltransferase concentration in men

Cited by 24 publications

References 32 publications

Plasma levels of lecithin:cholesterol acyltransferase and risk offuture coronary artery disease in apparently healthy men and women: aprospective case-control analysis nested in the EPIC-Norfolk populationstudy

Plasma levels of lecithin:cholesterol acyltransferase and risk offuture coronary artery disease in apparently healthy men and women: aprospective case-control analysis nested in the EPIC-Norfolk populationstudy

A Comparison of the Theoretical Relationship between HDL Size and the Ratio of HDL Cholesterol to Apolipoprotein A-I with Experimental Results from the Women's Health Study

Effects of lecithin: Cholesterol acyltransferase genotypes, enzyme levels, and activity on high-density lipoprotein levels

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