HDL-apolipoprotein A-I exchange is independently associated with cholesterol efflux capacity

Borja, Mark S.; Ng, Kit Fai; Irwin, Angela; Hong, Jaekyoung; Wu, Xing; Isquith, Daniel; Zhao, Xue Qiao; Prazen, Bryan J.; Gildengorin, Virginia; Oda, Michael N.; Vaisar, Tomáš

doi:10.1194/jlr.m059865

Cited by 40 publications

(56 citation statements)

References 55 publications

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“…Compared to normal, PUC values for sickle plasma were significantly different and lower (Figure 2(b)). A strong positive correlation (R 2 ¼ 0.743, P < 0.0001) was also observed between the ApoA-I concentration and the HDL-ApoA-I exchange rate parameter (%HAE, 34,35 ) in sickle plasma (Figure 3(a)). As measured by the amount of carbonyl groups, an increased level of oxidized proteins (including ApoA-I) was detected in sickle plasma (Figure 3(b)).…”

Section: Hdl-apoa-i Dysfunction In Sickle Plasmamentioning

confidence: 77%

“…34,35 When plasma is mixed with a lipid-free ApoA-I-spin labeled probe, the exchange with HDL will unquench the EPR signal of the spin probe. 34,35 In this study, we measured HDL-ApoA-I exchange at several plasma concentrations, by measuring the EPR signal obtained in the presence of increasing volumes of plasma (Figure 2). The slope of the linear regression fit of the EPR signal versus plasma volume defined the ApoA-I-PUC.…”

Section: Hdl-apoa-i Dysfunction In Sickle Plasmamentioning

confidence: 99%

“…ApoA-I is conformationally dynamic and lipid-free ApoA-I exchanges with ApoA-I bound to HDL particles, a process critical to HDL formation, maturation, and reverse cholesterol transport. [34][35][36][37] Lipid-free ApoA-I undergoes significant conformational changes when exchanging onto HDL particles. The addition of a nitroxide spin label permits this change to be monitored by EPR.…”

Section: Hdl-apoa-i Dysfunction In Sickle Plasmamentioning

confidence: 99%

“…ApoA-I is the major protein component of HDL particles, and lipid-free ApoA-I can exchange spontaneously with HDL-bound ApoA-I, permitting in vitro quantitation of HDL-ApoA-I exchange as a measure of HDL particle functionality in human plasma. [34][35][36][37] HDL-ApoA-I exchange was reduced in sickle plasma, indicating dysfunctionality of the sickle HDL and this decrease was more pronounced during vaso-occlusive episodes (VOE) of sickle patients even after they received RBC concentrate transfusion. Our data indicate that the highly oxidative environment of sickle blood induced sulfhydryl alterations of the essential components in both plasma and RBC to maintain CE formation.…”

Section: Introductionmentioning

confidence: 99%

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Featured Article: Alterations of lecithin cholesterol acyltransferase activity and apolipoprotein A-I functionality in human sickle blood

Soupène¹,

Borja²,

Borda³

et al. 2016

Exp Biol Med (Maywood)

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In sickle cell disease (SCD) cholesterol metabolism appears dysfunctional as evidenced by abnormal plasma cholesterol content in a subpopulation of SCD patients. Specific activity of the high density lipoprotein (HDL)-bound lecithin cholesterol acyltransferase (LCAT) enzyme, which catalyzes esterification of cholesterol, and generates lysoPC (LPC) was significantly lower in sickle plasma compared to normal. Inhibitory amounts of LPC were present in sickle plasma, and the red blood cell (RBC) lysophosphatidylcholine acyltransferase (LPCAT), essential for the removal of LPC, displayed a broad range of activity. The functionality of sickle HDL appeared to be altered as evidenced by a decreased HDL-Apolipoprotein A-I exchange in sickle plasma as compared to control. Increased levels of oxidized proteins including ApoA-I were detected in sickle plasma. In vitro incubation of sickle plasma with washed erythrocytes affected the ApoA-I-exchange supporting the view that the RBC blood compartment can affect cholesterol metabolism in plasma. HDL functionality appeared to decrease during acute vaso-occlusive episodes in sickle patients and was associated with an increase of secretory PLA 2 , a marker for increased inflammation. Simvastatin treatment to improve the anti-inflammatory function of HDL did not ameliorate HDL-ApoA-I exchange in sickle patients. Thus, the cumulative effect of an inflammatory and highly oxidative environment in sickle blood contributes to a decrease in cholesterol esterification and HDL function, related to hypocholesterolemia in SCD.

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Section: Hdl-apoa-i Dysfunction In Sickle Plasmamentioning

confidence: 77%

Section: Hdl-apoa-i Dysfunction In Sickle Plasmamentioning

confidence: 99%

Section: Hdl-apoa-i Dysfunction In Sickle Plasmamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Featured Article: Alterations of lecithin cholesterol acyltransferase activity and apolipoprotein A-I functionality in human sickle blood

Soupène¹,

Borja²,

Borda³

et al. 2016

Exp Biol Med (Maywood)

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show abstract

“…20,23 Freshly thawed plasma was mixed 1:4 with PBS (20 mM phosphate, 150 mM NaCl, pH 7.4) and 24% w/v PEG 6000 (Sigma) was added to a final concentration of 4%. Samples were centrifuged at 13,000 rpm for 10 minutes in a tabletop centrifuge at 4°C to remove apoB-containing lipoproteins.…”

Section: Participants and Methodsmentioning

confidence: 99%

Effects of aspirin in combination with EPA and DHA on HDL-C cholesterol and ApoA1 exchange in individuals with type 2 diabetes mellitus

Block

Holub

Abdolahi

et al. 2017

Prostaglandins, Leukotrienes and Essential Fatty Acids

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Background/Synopsis Low-dose aspirin is an effective drug for the prevention of cardiovascular disease (CVD) events but individuals with diabetes mellitus can be subject to ‘aspirin resistance’. Thus, aspirin’s effect in these individuals is controversial. Higher blood levels of seafood-derived omega-3 polyunsaturated fatty acids (ω3) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) also have beneficial effects in reducing risk of CVD events but few studies have examined the interaction of plasma EPA and DHA with aspirin ingestion. Objective/Purpose Our study examined the combinatory effects of EPA, DHA, and aspirin ingestion on HDL-cholesterol (HDL-C) and apoA-I exchange (shown to be associated with CVD event risk). Methods 30 adults with Type 2 diabetes mellitus ingested aspirin (81 mg/day) for 7 consecutive days, EPA+DHA (2.6g/day) for 28 days, then both for 7 days. Plasma was collected at baseline and at 5 subsequent visits including 4 hours after each aspirin ingestion. Mixed model methods were used to determine HDL-C-concentrations and apoA-I exchange compared to the baseline visit values. LOWESS curves were used for non-linear analyses of outcomes to help discern change patterns, which was followed by piecewise linear functions for formal testing of curvilinear relationships. Results Significant changes (p<0.05) compared to baseline in both HDL-C-concentrations and apoA-I exchange were present at different times. After 7 days of aspirin-only ingestion, apoA-I exchange was significantly modified by increasing levels of DHA concentration, with increased apoA-I exchange observed up until log(DHA) of 4.6 and decreased exchange thereafter (p=0.03). These LOWESS curve effects were not observed for EPA or HDL-C (p>0.05). Aspirin’s effects on apoA-I exchange were the greatest when EPA or DHA concentrations were moderate compared to high or low. Comparison of EPA, DHA, and EPA+DHA LOWESS curves, demonstrated that the majority of the effect is due to DHA. Conclusion Our results strongly suggest that plasma concentrations of EPA and DHA influence aspirin effects on lipid mediators of CVD event risk where their concentrations are most beneficial when moderate, not high or low. These effects on HDL-C cholesterol and apoA-I exchange are novel. Personalized dosing of DHA in those who take aspirin may be a beneficial option for patients with type 2 diabetes mellitus.

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Crosstalk Between Cholesterol, ABC Transporters, and PIP2 in Inflammation and Atherosclerosis

Gulshan

2023

Advances in Experimental Medicine and Biology

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HDL-apolipoprotein A-I exchange is independently associated with cholesterol efflux capacity

Cited by 40 publications

References 55 publications

Featured Article: Alterations of lecithin cholesterol acyltransferase activity and apolipoprotein A-I functionality in human sickle blood

Featured Article: Alterations of lecithin cholesterol acyltransferase activity and apolipoprotein A-I functionality in human sickle blood

Effects of aspirin in combination with EPA and DHA on HDL-C cholesterol and ApoA1 exchange in individuals with type 2 diabetes mellitus

Crosstalk Between Cholesterol, ABC Transporters, and PIP2 in Inflammation and Atherosclerosis

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