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

Low, Hann; Hoang, Anh; Forbes, Josephine M.; Thomas, Merlin C.; Lyons, Jasmine G.; Nestel, Paul J.; Bach, Leon Ashley; Sviridov, Dmitri

doi:10.1007/s00125-012-2570-9

Cited by 43 publications

(42 citation statements)

References 48 publications

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“…Nevertheless, we (Kralova Lesna et al, 2008) and others (Fadini et al, 2014;Low et al, 2012) have clearly shown that HDL cholesterol and ApoA1 concentrations do not necessarily correspond to the real capacity of RCT. Therefore, we included the direct determination of plasma-induced cholesterol efflux from human macrophages as an RCT measure.…”

Section: Introductionmentioning

confidence: 78%

Could human cold adaptation decrease the risk of cardiovascular disease?

Lesná

Rychlikova

Vávřová

et al. 2015

Journal of Thermal Biology

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Section: Introductionmentioning

confidence: 78%

Could human cold adaptation decrease the risk of cardiovascular disease?

Lesná

Rychlikova

Vávřová

et al. 2015

Journal of Thermal Biology

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“…38, 184 In a recent study, HDL and sera of diabetic subjects were found to display increased rather than decreased cholesterol efflux capacity, which correlated with CETP activity but not with AGE levels. 191 Neither showed AGE levels any association with macrophage reverse cholesterol transport in vivo of db/db mice or uremic mice. 191 HDLs enriched with either AGE in T2DM patients or with MDA in CAD patients failed to inhibit monocyte or neutrophil diapedesis through endothelial cells by suppressing VCAM-1 and intracellular adhesion molecule-1 expression.…”

Section: Hdl Dysfunctionmentioning

confidence: 91%

“…191 Neither showed AGE levels any association with macrophage reverse cholesterol transport in vivo of db/db mice or uremic mice. 191 HDLs enriched with either AGE in T2DM patients or with MDA in CAD patients failed to inhibit monocyte or neutrophil diapedesis through endothelial cells by suppressing VCAM-1 and intracellular adhesion molecule-1 expression. 38,192 Both the HDL of CAD patients and that of healthy subjects enriched with MDA bind to the scavenger receptor LOX-1 of endothelial cells.…”

Section: Hdl Dysfunctionmentioning

confidence: 91%

High-Density Lipoproteins

Annema

Eckardstein

2013

Circ J

144

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Low plasma levels of high-density lipoprotein (HDL) cholesterol are associated with increased risks of coronary artery disease (CAD). HDL particles exert many effects in vitro and in vivo that may protect arteries from chemical or biological harm or facilitate repair of injuries. Nevertheless, HDL has not yet been successfully exploited for therapy. One potential reason for this shortfall is the structural and functional complexity of HDL particles, which carry more than 80 different proteins and more than 200 lipid species as well as several microRNAs and other potentially bioactive molecules. This physiological heterogeneity is further increased in several inflammatory conditions that increase cardiovascular risk, including CAD itself but also diabetes mellitus, chronic kidney disease, and rheumatic diseases. The quantitative and qualitative modifications of the proteome and lipidome, as well as the resulting loss of functions or gain of dysfunctions, are not recovered by the biomarker HDL-cholesterol. As yet the relative importance of the many physiological and pathological activities of normal and dysfunctional HDL, respectively, for the pathogenesis of atherosclerosis is unknown. The answer to this question, as well as detailed knowledge of structure-function-relationships of HDL-associated molecules, is a prerequisite to exploit HDL for the development of anti-atherogenic drugs as well as of diagnostic biomarkers for the identification, personalized treatment stratification, and monitoring of patients at increased cardiovascular risk. 2433Multifunctional but Vulnerable HDL munication of results. 15 As yet, clinical and epidemiological studies have come to discrepant and inconsistent conclusions on the prognostic performance of HDL subclasses differentiated by size. 14,20-24 Sometimes the associations of cardiovascular risk with the various HDL subclass concentrations were not stronger than with HDL-C, 20,21 and even if so, the associations with size were discrepant: significant associations with risk of cardiovascular events or stroke were found for small HDL in some studies, 22,23 but for medium-sized HDL 21,23 or large HDL 14,20,21,24 in others.Previous proteomic, lipidomic, and transcriptomic studies revealed a much greater structural complexity of HDLs: 80 different proteins, 25,26 more than 200 lipid species, 27,28 and several microRNAs 29,30 have been identified in HDL isolated from plasma by either ultracentrifugation, gel filtration, or immunoaffinity chromatography (Figure 1). Among the proteins, apoA-II is present in HDLs at the highest concentration after that of apoA-I and has been investigated for its cardiovascular risk association by several studies. In contrast to initial findings, large prospective studies did not find any significant differences in the risk association between apoA-II-containing and apoA-II-free HDL. [15][16][17] Despite their much lower concentrations relative to the 2 major proteins apoA-I and apoA-II and relative to the major lipids, many quantitatively minor componen...

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“…13,14 In one small study, CEC to apoB-depleted plasma moderately correlated with CEC to isolated HDL (r=0.46, p<0.02) but was not correlated at all with CEC to whole plasma (p>0.2). 15 Ascertaining the specific methodology used to assess CEC is critical when evaluating the reported findings in human studies. Correlations between CEC and other lipid markers can vary widely whether using whole vs. apoB-depleted plasma/serum as the cholesterol acceptor.…”

Section: Measuring Cholesterol Efflux Capacity (Cec) In Humansmentioning

confidence: 99%

High-Density Lipoprotein Function Measurement in Human Studies: Focus on Cholesterol Efflux Capacity

Rohatgi

2015

Progress in Cardiovascular Diseases

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A low plasma level of high-density lipoprotein (HDL) cholesterol (HDL-C) is a major risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). However, several observations have highlighted the shortcomings of using cholesterol content as the sole reflection of HDL metabolism. In particular, several large randomized controlled trials of extended release niacin and cholesteryl-ester transfer protein (CETP) inhibitors on background statin therapy have failed to show improvement in ASCVD outcomes despite significant increases in HDL-C. Reverse cholesterol transport (RCT) is the principal HDL function that impacts macrophage foam cell formation and other functions such as endothelial activation of endothelial nitric oxide synthase, monocyte adhesion, and platelet aggregation. Cholesterol efflux from macrophages to plasma/serum reflects the first critical step of RCT and is considered a key anti-atherosclerotic function of HDL. Whether this function is operative in humans remains to be seen, but recent studies assessing cholesterol efflux in humans suggest that the cholesterol efflux capacity (CEC) of human plasma or serum is a potent marker of ASCVD risk. This review describes the methodology of measuring CEC ex vivo from human samples and the findings to date linking CEC to human disease. Studies to date confirm that CEC can be reliably measured using stored human blood samples as cholesterol acceptors and suggest that CEC may be a promising new biomarker for atherosclerotic and metabolic diseases. Further studies are needed to standardize measurements and clarify the role CEC may play in predicting risk of developing disease and response to therapies.

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

Cited by 43 publications

References 48 publications

Could human cold adaptation decrease the risk of cardiovascular disease?

Could human cold adaptation decrease the risk of cardiovascular disease?

High-Density Lipoproteins

High-Density Lipoprotein Function Measurement in Human Studies: Focus on Cholesterol Efflux Capacity

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