HDL from CETP-deficient subjects shows enhanced ability to promote cholesterol efflux from macrophages in an apoE- and ABCG1-dependent pathway

Matsuura, Fumihiko; Wang, Nan; Chen, Wengen; Tall, Alan R.

doi:10.1172/jci27602

Cited by 264 publications

(214 citation statements)

References 47 publications

(42 reference statements)

Supporting

Mentioning

196

Contrasting

Order By: Relevance

“…This is consistent with several reports that smaller particles are more active in cholesterol efflux [40,41], and our recent finding of a correlation between the ability of plasma to support cholesterol efflux and CETP concentration [12]. It is, however, inconsistent with findings that functionality of HDL particles formed as a result of inhibition of CETP was not impaired [42,43]. The only chemical modification of HDL known to increase its capacity to support cholesterol efflux is oxidative tyrosilation [44]; this was not tested in this study.…”

Section: Discussionsupporting

confidence: 88%

Advanced glycation end-products (AGEs) and functionality of reverse cholesterol transport in patients with type 2 diabetes and in mouse models

et al. 2012

View full text Add to dashboard Cite

Aims/hypothesis We investigated the contribution of AGEs to the impairment of reverse cholesterol transport (RCT) variables in diabetic individuals and in two animal models of diabetic obesity and of renal impairment. Methods The capacity of plasma and HDL from 26 individuals with moderately controlled type 2 diabetes to support cholesterol efflux was compared with 26 age-and sexmatched individuals without diabetes. We also compared the rates of RCT in vivo in two animal models: db/db mice and mice with chronic renal failure. Results Diabetic individuals had characteristic dyslipidaemia and higher levels of plasma AGEs. The capacity of whole plasma, ApoB-depleted plasma and isolated HDL to support cholesterol efflux was greater for diabetic patients compared with controls despite their lower HDL-cholesterol levels. The capacity of plasma to support cholesterol efflux correlated with plasma levels of cholesteryl ester transfer protein and levels of ApoB, but not with levels of AGE. RCT was severely impaired in db/db mice despite elevated HDL-cholesterol levels and no change in AGE concentration, whereas RCT in uraemic mice was unaffected despite elevated AGE levels. Conclusions/interpretation AGEs are unlikely to contribute significantly to the impairment of RCT in type 2 diabetes.

show abstract

Section: Discussionsupporting

confidence: 88%

Advanced glycation end-products (AGEs) and functionality of reverse cholesterol transport in patients with type 2 diabetes and in mouse models

et al. 2012

View full text Add to dashboard Cite

show abstract

“…LCAT activity may induce net cholesterol efflux via a non-specific cholesterol exchange mechanism (33). Very recently, it has been demonstrated that the presence of LCAT and apo E on a-HDL particles is important for cholesterol efflux out of macrophages (34). In our study, cholesterol efflux from fibroblasts was independently related both to plasma EST and to apo E.…”

Section: Discussionsupporting

confidence: 56%

Fibroblast cholesterol efflux to plasma from metabolic syndrome subjects is not defective despite low high-density lipoprotein cholesterol

Dullaart¹,

Groen

Dallinga‐Thie

et al. 2008

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective: We tested whether in metabolic syndrome (MetS) subjects the ability of plasma to stimulate cellular cholesterol efflux, an early step in the anti-atherogenic reverse cholesterol transport pathway, is maintained despite low high-density lipoprotein (HDL) cholesterol. Design: In 76 subjects with and 94 subjects without MetS based on the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, we determined plasma (apo)lipoproteins, pre-b-HDL formation, phospholipid transfer protein (PLTP) activity, cholesterol esterification (EST), cholesteryl ester transfer (CET), adiponectin, and the ability of plasma from each subject to stimulate cholesterol efflux out of cultured fibroblasts obtained from a single donor. Results: Apo E, PLTP activity, EST, and CET were higher (PZ0.04 to !0.001), whereas adiponectin was lower in MetS subjects (P!0.01). Pre-b-HDL and pre-b-HDL formation were not different between subjects with and without MetS. Cellular cholesterol efflux to plasma from MetS subjects was slightly higher versus plasma from subjects without MetS (8.8G1.0 vs 8.5G0.9%, PZ0.05), but the difference was not significant after age, sex, and diabetes adjustment. Cellular cholesterol efflux was positively related to pre-b-HDL formation, EST, PLTP activity, and apo E (P!0.05 for all by multiple linear regression analysis), without an independent association with MetS and diabetes status. Conclusions: The ability of plasma from MetS subjects to promote fibroblast cholesterol efflux is not defective, although HDL cholesterol is decreased. Higher cholesterol esterification, PLTP activity, and apo E levels may contribute to the maintenance of cholesterol efflux in MetS.European Journal of Endocrinology 158 53-60

show abstract

“…therein). In plasma, apoE facilitates CE core expansion in HDL and thereby plays an important role in HDL metabolism, particularly in case of cholesterol ester transfer protein deficiency (33,34). Thus, apoE-containing HDL, which may be generated during lipolysis of TG-rich proteins, are important players in lipoprotein metabolism.…”

Section: Discussionmentioning

confidence: 99%

Thermal Transitions in Human Very-Low-Density Lipoprotein: Fusion, Rupture, and Dissociation of HDL-like Particles

et al. 2007

View full text Add to dashboard Cite

Very low-density lipoproteins (VLDL) are metabolic precursors of low-density lipoproteins (LDL) and a risk factor for atherosclerosis. Human VLDL are heterogeneous complexes containing triacylglyceride-rich apolar lipid core and polar surface comprised of phospholipids, a nonexchangeable apolipoprotein B, and exchangeable apolipoproteins E and Cs. We report the first stability study of VLDL. Circular dichroism and turbidity data reveal an irreversible heat-induced VLDL transition that involves formation of larger particles and repacking of apolar lipids but no global protein unfolding. Heating rate effect on the melting temperature indicates a kinetically controlled reaction with high activation energy, E a . Arrhenius analysis of the turbidity data reveals two kinetic phases with E a =53±7 kcal/mol that correspond to distinct morphological transitions observed by electron microscopy. One transition involves VLDL fusion, partial rupture and dissociation of small spherical particles (d=7-15 nm), and another involves complete lipoprotein disintegration and lipid coalescence into droplets accompanied by dissociation of apolipoprotein B. The small particles, which are unique to VLDL denaturation, are comparable in size and density to high-density lipoproteins (HDL); they have apolar lipid core and polar surface comprised of exchangeable apolipoproteins (E and possibly Cs) and phospholipids. We conclude that, similar to HDL and LDL, VLDL are stabilized by kinetic barriers that prevent particle fusion and rupture and decelerate spontaneous inter-conversion among lipoprotein classes and subclasses. In addition to fusion, VLDL disruption involves transient formation of HDL-like particles that may mimic protein exchange among VLDL and HDL pools in plasma.Plasma lipoproteins, including high-, low-, intermediate-, and very-low density lipoproteins (HDL, LDL, IDL and VLDL), are macromolecular complexes of lipids and proteins (termed apolipoproteins) that mediate lipid transport and metabolism and are central in the development of coronary artery disease. HDL are anti-atherogenic, LDL are pro-atherogenic, and VLDL are not only direct metabolic precursors of LDL but also an independent risk factor for atherosclerosis (1)(2)(3)(4)(5)(6)(7)(8). VLDL are the major carriers of triacylglycerides (TG) in plasma. Human VLDL form heterogeneous population of spherical particles that contain apolar core comprised mainly of TG and cholesterol esters (CE) and polar surface comprised of cholesterol-containing phospholipid monolayer and proteins. The proteins include one copy of non-exchangeable apolipoprotein B (apoB, 550 kD) and multiple copies of exchangeable apolipoproteins, mainly apoE (34 kD) and apoCs (6-9 kD), that comprise over 50% of the total VLDL protein content. Metabolic remodeling by lipolytic enzymes converts VLDL into LDL that contain apoB as their sole protein, while the dissociated apoE and apoCs enter the HDL pool (2,4). Structural Our recent thermal and chemical denaturation analyses have shown that HDL and LDL...

show abstract

HDL from CETP-deficient subjects shows enhanced ability to promote cholesterol efflux from macrophages in an apoE- and ABCG1-dependent pathway

Cited by 264 publications

References 47 publications

Advanced glycation end-products (AGEs) and functionality of reverse cholesterol transport in patients with type 2 diabetes and in mouse models

Advanced glycation end-products (AGEs) and functionality of reverse cholesterol transport in patients with type 2 diabetes and in mouse models

Fibroblast cholesterol efflux to plasma from metabolic syndrome subjects is not defective despite low high-density lipoprotein cholesterol

Thermal Transitions in Human Very-Low-Density Lipoprotein: Fusion, Rupture, and Dissociation of HDL-like Particles

Contact Info

Product

Resources

About