Cholesterol efflux from Fu5AH hepatoma cells induced by plasma of subjects with or without coronary artery disease and non-insulin-dependent diabetes: importance of LpA-I:A-II particles and phospholipid transfer protein

Syvänne, Mikko; Castro, Graciela; Dengremont, Catherine; Geitere, Catherine De; Jauhiainen, Matti; Ehnholm, Christian; Michelagnoli, Silvia; Franceschini, Guido; Kahri, Juhani; Taskinen, Marja‐Riitta

doi:10.1016/s0021-9150(96)05962-x

Cited by 102 publications

(75 citation statements)

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“…With respect to CETP mass we did not measure CETP activity Insulin sensitivity influences cholesterol efflux P Nestel et al although it is recognised that mass and activity tend to be significantly correlated. Several previous studies had reported diminished cholesterol efflux in vitro when cells were incubated with plasma or LpA-I derived from diabetic subjects 2,3 , in contrast to the present study, which showed increased capacity of plasmas from IR subjects to support cholesterol efflux. Our study appears to be the first to have differentiated efflux capacity between plasmas from subjects with insulin resistance and insulin sensitivity.…”

Section: Discussioncontrasting

confidence: 99%

“…We do not have an explanation for the apparent contradiction between the findings of increased RCT in IR subjects and that of diminished cholesterol efflux reported earlier for plasmas from diabetic subjects. 2,3 Further, the first large-scale study of the capacity of plasmas (depleted of apoB lipoproteins) to support in vitro cholesterol efflux has shown to be diminished in patents with proven coronary artery disease or increased carotid intima-media thickening. 1 The authors could not explain what factors beside HDL may have been deficient in the plasmas of those subjects as low HDL itself could not explain the findings.…”

Section: Discussionmentioning

confidence: 99%

“…1 Cholesterol efflux measured in vitro has also been found to be diminished when cells were incubated with plasma or isolated apolipoprotein A-I from type 2 diabetic subjects. Syvanne et al 2 found that plasmas from diabetic men especially if they also suffered from coronary artery disease induced a diminished efflux from Fu5AH hepatoma cells. Further, the usual positive relationship between LpA-I concentration in plasma and efflux was absent, although such an association did exist between efflux and LpA-I:A-II HDL particles.…”

Section: Introductionmentioning

confidence: 99%

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Cholesterol efflux from macrophages is influenced differentially by plasmas from overweight insulin-sensitive and -resistant subjects

et al. 2011

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Objective: In vitro measurements of cholesterol efflux from macrophages have recently been shown to associate with cardiovascular risk. We investigated whether cholesterol efflux from macrophages incubated with plasmas from overweight/ obese subjects with metabolic syndrome was influenced by the presence of insulin resistance. Methods: Plasmas were obtained from 47 men and women with metabolic syndrome, of whom 25 were found to be insulin resistant (IR) and 22 insulin sensitive (IS) (Matsuda, De Fronzo equation based on oral glucose tolerance test). Activated human macrophage THP-1 cells in which cholesterol had been radiolabelled were incubated with the subjects' plasmas to allow calculation of % cholesterol efflux. Results: Body mass index and waist measurements, as well as plasma lipid levels, did not differ between the two groups. Homeostatic model assessment-insulin resistance value as well as plasma insulin and leptin concentrations were higher in IR subjects. Cholesterol efflux was found to be significantly greater with plasmas from IR subjects (9.1%) than from IS subjects (6.7%) (P ¼ 0.005). Further, cholesterol efflux was significantly inversely associated with insulin sensitivity index (Po0.001), directly with arterial insulin concentration (Po0.001) and directly with cholesteryl ester transfer protein (CETP) mass (P ¼ 0.044). Conclusion: Plasmas from overweight subjects with insulin resistance induced greater in vitro cholesterol efflux compared with IS subjects. Efflux inversely correlated with insulin sensitivity suggesting an increase in reverse cholesterol transport in the IR state that may lead to greater transfer of cholesterol to apoB lipoproteins from high-density lipoproteins via CETP as a factor in the association between IR and atherosclerosis.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cholesterol efflux from macrophages is influenced differentially by plasmas from overweight insulin-sensitive and -resistant subjects

et al. 2011

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“…As expected there was a consistent decrease in LpA-I:A-II particles in Type 2 diabetic patients. We also found that the ability of plasma from Type 2 diabetic subjects to promote cholesterol efflux in vitro from hepatoma cells was related to LpA-I:A-II concentrations rather than to LpA-I concentrations [143]. Thus Type 2 diabetic subjects showed a deficiency of Lp:A-I mediated reverse-cholesterol transport.…”

Section: Metabolic Alterations Of Hdl Subclasses In Type 2 Diabetesmentioning

confidence: 65%

Diabetic dyslipidaemia: from basic research to clinical practice*

2003

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The recognition that the increase of plasma triglyceride rich lipoproteins (TRLs) is associated with multiple alterations of other lipoproteins species that are potentially atherogenic has expanded the picture of diabetic dyslipidaemia. The discovery of heterogeneity within major lipoprotein classes VLDL, LDL and HDL opened new avenues to reveal the specific pertubations of diabetic dyslipidaemia. The increase of large VLDL 1 particles in Type 2 diabetes initiates a sequence of events that generates atherogenic remnants, small dense LDL and small dense HDL particles. Together these components comprise the atherogenic lipid triad. Notably the malignant nature of diabetic dyslipidaemia is not completely shown by the lipid measures used in clinical practice. The key question is what are the mechanisms behind the increase of VLDL 1 particles in diabetic dyslipidaemia? Despite the advances of recent years, our understanding of VLDL assembly and secretion is still surprisingly incomplete. To date it is still unclear how the liver is able to regulate the amount of triglycerides incorporated into VLDL particles to produce either VLDL 1 or VLDL 2 particles. The current evidence suggests that the machinery driving VLDL assembly in the liver includes (i) low insulin signalling via PI-3 kinase pathway that enhances lipid accumulation into "nascent" VLDL particles (ii) up-regulation of SREBP-1C that stimulates de novo lipogenesis and (iii) excess availability of "polar molecules" in hepatocytes that stabilizes apo B 100. Recent data suggest that all these steps could be fundamentally altered in Type 2 diabetes explaining the overproduction of VLDL apo B as well as the ability of insulin to suppress VLDL 1 apo B production in Type 2 diabetes.Recent discoveries have established the transcription factors including PPARs, SREBP-1 and LXRs as the key regulators of lipid assembly in the liver. These observations suggest these factors as a new target to tailor more efficient drugs to treat diabetic dyslipidaemia. [Diabetologia (2003) 46:733-749]

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“…7 Therefore, the use of whole serum instead of isolated lipoprotein fractions would provide an ideal tool to evaluate the individual capacity to promote cell cholesterol efflux. 8 This approach has the advantage that all of the potential factors affecting efflux are present in the experimental setting, and therefore seems particularly suitable to correlate the efficiency of the earliest step in RCT to atherosclerosis susceptibility in subjects, 9,10 or animal models at different risks of cardiovascular disease. 11,12 ApoA-I Milano (A-I M ) is the first described mutant of human apolipoproteins.…”

mentioning

confidence: 99%

Increased Cholesterol Efflux Potential of Sera From ApoA-I _Milano Carriers and Transgenic Mice

Franceschini

Calabresi

Chiesa

et al. 1999

ATVB

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115

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Cholesterol efflux from Fu5AH hepatoma cells induced by plasma of subjects with or without coronary artery disease and non-insulin-dependent diabetes: importance of LpA-I:A-II particles and phospholipid transfer protein

Cited by 102 publications

References 54 publications

Cholesterol efflux from macrophages is influenced differentially by plasmas from overweight insulin-sensitive and -resistant subjects

Cholesterol efflux from macrophages is influenced differentially by plasmas from overweight insulin-sensitive and -resistant subjects

Diabetic dyslipidaemia: from basic research to clinical practice*

Increased Cholesterol Efflux Potential of Sera From ApoA-I _Milano Carriers and Transgenic Mice

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Cholesterol efflux from Fu5AH hepatoma cells induced by plasma of subjects with or without coronary artery disease and non-insulin-dependent diabetes: importance of LpA-I:A-II particles and phospholipid transfer protein

Cited by 102 publications

References 54 publications

Cholesterol efflux from macrophages is influenced differentially by plasmas from overweight insulin-sensitive and -resistant subjects

Cholesterol efflux from macrophages is influenced differentially by plasmas from overweight insulin-sensitive and -resistant subjects

Diabetic dyslipidaemia: from basic research to clinical practice*

Increased Cholesterol Efflux Potential of Sera From ApoA-I Milano Carriers and Transgenic Mice

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Product

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Increased Cholesterol Efflux Potential of Sera From ApoA-I _Milano Carriers and Transgenic Mice