ATP binding cassette G1-dependent cholesterol efflux during inflammation

Beer, Maria C. de; Ji, Ailing; Jahangiri, Anisa; Vaughan, Ashley M.; Beer, Frederick C. de; Westhuyzen, Deneys R. van der; Webb, Nancy R.

doi:10.1194/jlr.m012328

Cited by 36 publications

(27 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A recent study of type 2 diabetics found negative association of SAA levels with SRBI-mediated cholesterol effl ux capacity and no association with ABCG1-mediated cholesterol effl ux capacity in 500 diabetic and nondiabetic subjects, although clinical relevance of these assays of cholesterol effl ux capacity is unknown ( 67 ). In contrast, another study suggested that infl ammation-induced increase in the phospholipid content of HDL modestly improved the ability of HDL to promote sterol effl ux by the ABCG1 pathway ( 55 ). However, effl ux by this pathway only contributes about one-fourth of the effl ux from macrophages to HDL ( 68 ).…”

Section: Discussionmentioning

confidence: 96%

“…Previous studies demonstrate that infl ammation markedly alters the lipid composition of plasma and HDL, and that lipids can contribute to the sterol effl ux capacity of HDL by certain pathways (e.g., ABCG1) ( 49,55,56 ). We therefore quantifi ed levels of specifi c lipid classes in plasma and in HDL of WT and Saa1 / 2 Ϫ / Ϫ mice, with and without infl ammation.…”

Section: Infl Ammation-induced Alterations In Plasma and Hdl Lipid Comentioning

confidence: 99%

See 1 more Smart Citation

Inflammatory remodeling of the HDL proteome impairs cholesterol efflux capacity

Vaisar

Tang

Babenko

et al. 2015

Journal of Lipid Research

164

132

View full text Add to dashboard Cite

Journal of Lipid Research Volume 56, 2015 1519have triggered intense interest in targeting HDL for therapeutic intervention. Several recent observations have cast doubt on the hypotheses that HDL-C levels relate to CAD risk in humans and that elevating HDL-C is therapeutic ( 3, 4 ). For example, genetic variations that alter levels of HDL-C do not always associate with CAD risk, and interventions that elevate HDL-C do not necessarily reduce cardiovascular events in humans with established CAD ( 5 ). Taken together, these observations indicate that HDL is complex and that simply quantifying HDL-C might be a poor way to assess HDL function ( 6, 7 ).The ability of HDL (or serum HDL, serum depleted of apoB-containing lipoproteins) to promote sterol effl ux from cultured macrophages incubated with radiolabeled cholesterol can vary markedly, despite similar levels of HDL-C and apoA-I ( 8 ). Therefore, HDL-C is not necessarily the major determinant of HDL's macrophage sterol effl ux capacity in this system. Importantly, the effl ux capacity of serum HDL is lower in individuals with prevalent CAD ( 9-11 ). A recent study of a large cohort, initially free of CAD, demonstrated that sterol effl ux associates strongly and negatively with the risk of future cardiac events ( 12 ). This association was strengthened by multivariate adjustment, suggesting that impaired HDL function affects incident cardiovascular risk by processes distinct from those involving HDL-C, LDL-cholesterol (LDL-C), and other traditional lipid risk factors. Together, these observations indicate that the sterol effl ux capacity of HDL might be a marker, and perhaps a mediator, of atherosclerotic Abstract Recent studies demonstrate that HDL's ability to promote cholesterol effl ux from macrophages associates strongly with cardioprotection in humans independently of HDL-cholesterol (HDL-C) and apoA-I, HDL's major protein. However, the mechanisms that impair cholesterol effl ux capacity during vascular disease are unclear. Infl ammation, a well-established risk factor for cardiovascular disease, has been shown to impair HDL's cholesterol effl ux capacity. We therefore tested the hypothesis that HDL's impaired effl ux capacity is mediated by specifi c changes of its protein cargo. Humans with acute infl ammation induced by low-level endotoxin had unchanged HDL-C levels, but their HDL-C effl ux capacity was signifi cantly impaired. Proteomic analyses demonstrated that HDL's cholesterol effl ux capacity correlated inversely with HDL content of serum amyloid A (SAA)1 and SAA2. In mice, acute infl ammation caused a marked impairment of HDL-C effl ux capacity that correlated with a large increase in HDL SAA. In striking contrast, the effl ux capacity of mouse infl ammatory HDL was preserved with genetic ablation of SAA1 and SAA2. Our observations indicate that the infl ammatory impairment of HDL-C effl ux capacity is due in part to SAA-mediated remodeling of HDL's protein cargo. -Vaisar, T

show abstract

Section: Discussionmentioning

confidence: 96%

Section: Infl Ammation-induced Alterations In Plasma and Hdl Lipid Comentioning

confidence: 99%

Inflammatory remodeling of the HDL proteome impairs cholesterol efflux capacity

Vaisar

Tang

Babenko

et al. 2015

Journal of Lipid Research

164

132

View full text Add to dashboard Cite

show abstract

“…In line with our observation, it was recently demonstrated that alterations in phospholipid content and not the presence of SAA in human HDL impaired the ability of acute phase HDL to promote cholesterol efflux. 36 In plasma, HDL undergoes a series of changes that are mediated by cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP). CETP mediates the exchange of HDL-associated cholesteryl esters with triglycerides from apoB-containing lipoproteins, whereas PLTP transfers phospholipids and free cholesterol from triglyceride-rich lipoproteins to HDL.…”

Section: Discussionmentioning

confidence: 99%

Uremia Alters HDL Composition and Function

Holzer

Birner‐Gruenberger

Stojaković

et al. 2011

Journal of the American Society of Nephrology

250

256

View full text Add to dashboard Cite

Functional impairment of HDL may contribute to the excess cardiovascular mortality experienced by patients with renal disease, but the effect of advanced renal disease on the composition and function of HDL is not well understood. Here, we used mass spectrometry and biochemical analyses to study alterations in the proteome and lipid composition of HDL isolated from patients on maintenance hemodialysis. We identified a significant increase in the amount of acute phase protein serum amyloid A1, albumin, lipoprotein-associated phospholipase A2, and apoC-III composing uremic HDL. Furthermore, uremic HDL contained reduced phospholipid and increased triglyceride and lysophospholipid. With regard to function, these changes impaired the ability of uremic HDL to promote cholesterol efflux from macrophages. In summary, the altered composition of HDL in renal disease seems to inhibit its cardioprotective properties. Assessing HDL composition and function in renal disease may help identify patients at increased risk for cardiovascular disease.

show abstract

“…Cellular cholesterol efflux experiments in ABCG1-inducible BHK cells were carried out essentially as described (38). Cells (70% confluent) in 12-well plates were labeled with 0.2 Ci/ml [ …”

Section: Cellular Cholesterol Efflux Determinationmentioning

confidence: 99%