scholarly journals Reactive Dicarbonyl Scavenging Effectively Reduces MPO-Mediated Oxidation of HDL and Preserves HDL Atheroprotective Functions

2019 ◽  
Author(s):  
Jiansheng Huang ◽  
Patricia G. Yancey ◽  
Huan Tao ◽  
Mark Borja ◽  
Loren Smith ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Adduct Formation ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Dependent Manner ◽  
Cholesterol Efflux Capacity ◽  
Hdl Function ◽  
Impaired Ability ◽  
Anti Inflammatory ◽  
Mediated Oxidation

AbstractHigh-density lipoprotein (HDL) is atheroprotective by mediating cholesterol efflux, anti-inflammatory, and anti-oxidation functions. Atheroprotective functions of HDL are related to the activity of HDL-associated enzymes such as paraoxonase 1 (PON1). We examined the impact of inhibition of myeloperoxidase (MPO)-mediated HDL oxidation by PON1 on HDL malondialdehyde (MDA) content and HDL function. In the presence of PON1, crosslinking of apoAI in response to MPO-mediated oxidation of HDL was abolished and MDA-HDL adduct levels were decreased. In addition, PON1 prevented the impaired cholesterol efflux capacity of MPO-oxidized HDL from Apoe-/- macrophages. Direct modification of HDL with MDA increased apoAI crosslinking and reduced the cholesterol efflux capacity in a dose dependent manner. In addition, MDA modification of HDL reduced its anti-inflammatory function compared to native HDL as the expression of IL-1β and IL6 increased by 3-(p<0.05) and 1.8-fold (p<0.05) in Apoe-/- macrophages in response to LPS. MDA-HDL also had impaired ability to increase PON1 activity. Importantly, HDL from subjects with familial hypercholesterolemia (FH-HDL) versus controls had increased MDA-apoAI adducts, and normalization of the PON1 activity to PON1 mass revealed a 24 % (p<0.05) decrease in specific activity indicating that PON1 activity is also impaired in FH. Consistent with the impaired PON1 activity and increased MDA-apoAI, FH-HDL induced a pro-inflammatory response in Apoe-/- macrophages compared to incubation with LPS alone. FH-HDL versus control HDL also had an impaired ability to promote cholesterol efflux from Apoe-/- macrophages. Interestingly, reactive dicarbonyl scavengers effectively abolished MPO-mediated apoAI crosslinking, MDA adduct formation, and improved cholesterol efflux capacity. Importantly, in vivo treatment of hypercholesterolemic mice with reactive dicarbonyl scavengers effectively reduced MDA-HDL adduct formation and increased PON1 activity and HDL cholesterol efflux capacity, supporting a therapeutic potential of reactive carbonyl scavenging in maintaining HDL function.

scholarly journals Reactive Dicarbonyl Scavenging Effectively Reduces MPO-Mediated Oxidation of HDL and Restores PON1 Activity

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1937 ◽  
Author(s):  
Jiansheng Huang ◽  
Patricia G. Yancey ◽  
Huan Tao ◽  
Mark S. Borja ◽  
Loren E. Smith ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Adduct Formation ◽  
Paraoxonase 1 ◽  
High Density Lipoproteins ◽  
Pon1 Activity ◽  
Cholesterol Efflux Capacity ◽  
Hdl Function ◽  
Impaired Ability ◽  
The Impact ◽  
Mediated Oxidation

Atheroprotective functions of high-density lipoproteins (HDL) are related to the activity of HDL-associated enzymes such as paraoxonase 1 (PON1). We examined the impact of inhibition of myeloperoxidase (MPO)-mediated HDL oxidation by PON1 on HDL malondialdehyde (MDA) content and HDL function. In the presence of PON1, crosslinking of apoAI in response to MPO-mediated oxidation of HDL was abolished, and MDA-HDL adduct levels were decreased. PON1 prevented the impaired cholesterol efflux capacity of MPO-oxidized HDL from Apoe−/− macrophages. Direct modification of HDL with MDA increased apoAI crosslinking and reduced the cholesterol efflux capacity. MDA modification of HDL reduced its anti-inflammatory function compared to native HDL. MDA-HDL also had impaired ability to increase PON1 activity. Importantly, HDL from subjects with familial hypercholesterolemia (FH-HDL) versus controls had increased MDA-apoAI adducts, and PON1 activity was also impaired in FH. Consistently, FH-HDL induced a pro-inflammatory response in Apoe−/− macrophages and had an impaired ability to promote cholesterol efflux. Interestingly, reactive dicarbonyl scavengers, including 2-hydroxybenzylamine (2-HOBA) and pentyl-pyridoxamine (PPM), effectively abolished MPO-mediated apoAI crosslinking, MDA adduct formation, and improved cholesterol efflux capacity. Treatment of hypercholesterolemic mice with reactive dicarbonyl scavengers reduced MDA-HDL adduct formation and increased HDL cholesterol efflux capacity, supporting the therapeutic potential of reactive carbonyl scavenging for improving HDL function.

Abstract 576: Salicylamine, A γ-ketoaldehyde Scavenger, Improves HDL Function and Reduces Atherosclerosis in Apoe Deficient Mice

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Jiansheng Huang ◽  
Patricia Yancey ◽  
Lei Ding ◽  
Youmin Zhang ◽  
John Oates ◽  
...  
Keyword(s):  
Western Blot ◽  
Cholesterol Efflux ◽  
Adduct Formation ◽  
Molar Ratio ◽  
Atherosclerotic Cardiovascular Disease ◽  
Dependent Manner ◽  
Cholesterol Accumulation ◽  
Cholesterol Efflux Capacity ◽  
Hdl Function ◽  
The Impact

Background: Lipid peroxidation products impair the cholesterol efflux capacity of high-density lipoprotein (HDL) and promote the development of atherosclerosis. The impact of inhibition of malondialdehyde (MDA)-HDL adduct formation by scavengers on HDL function and whether small molecule aldehyde scavengers protect against the development of atherosclerosis was examined. Methods and Results: Western blot analysis of ApoAI revealed that the amount of ApoAI crosslinking increased with MDA concentration. In the presence of LPS, MDA-HDL (HDL modified by 1mM MDA) versus control HDL stimulated 2- and 1.8-fold more expression of TNF-α and IL-1β in Apoe-/- macrophages demonstrating that MDA-HDL has reduced anti-inflammatory function. HDL-mediated macrophage cholesterol efflux was decreased by ~ 42%, 55%, 70%, and 80%, respectively, for HDL modified with 0.125 mM, 0.25 mM, 0.5 mM, and 1mM MDA, demonstrating that MDA modification of HDL affects its cholesterol efflux capacity in a dose dependent manner. Analysis by Western blot demonstrated that 5mM of salicylamine (SAM) and 5mM of pentylpyridoxamine (PPM), γ-ketoaldehyde scavengers, attenuated MDA mediated crosslinking of apoA-I in HDL (molar ratio of MDA and HDL is 1:5) by 60% and 80 % (P<0.05), respectively. Both SAM and PPM maintained the cholesterol efflux capacity of MDA treated HDL in Apoe-/- macrophages. In addition, pretreatment of LDL with SAM prevented MDA-ApoB adduct formation, and compared to incubation with LDL containing MDA-ApoB adducts, SAM treatment resulted in 57% less cholesterol accumulation in J774 macrophages. Importantly, administration of the ketoaldehyde scavenger, SAM, versus the nonreactive analogue, 4-SAM, to Apoe-/- mice consuming a Western diet for 16 weeks reduced the extent of proximal aortic atherosclerosis by 28% (P<0.05). Conclusions: Treatment with salicylamine, a γ-ketoaldehyde scavenger: 1) inhibits MDA-ApoA1 adduct formation thereby preserving HDL cholesterol efflux capacity; 2) prevents MDA-apoB100 formation resulting in less macrophage cholesterol accumulation; 3) reduces atherosclerosis in Apoe -/- mice. These results support the therapeutic potential of salicylamine in the treatment of atherosclerotic cardiovascular disease.

scholarly journals IL-1 Inhibition and Function of the HDL-Containing Fraction of Plasma in Patients with Stages 3 to 5 CKD

2019 ◽  
Vol 14 (5) ◽  
pp. 702-711 ◽  
Author(s):  
Adriana M. Hung ◽  
Yohei Tsuchida ◽  
Kristen L. Nowak ◽  
Sudipa Sarkar ◽  
Michel Chonchol ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Systemic Inflammation ◽  
Cholesterol Efflux ◽  
Superoxide Production ◽  
Receptor Protein ◽  
Maintenance Hemodialysis ◽  
Cholesterol Efflux Capacity ◽  
Cellular Expression ◽  
Hdl Function ◽  
Anti Inflammatory

Background and objectivesSystemic inflammation modulates cardiovascular disease risk and functionality of HDL in the setting of CKD. Whether interventions that modify systemic inflammation can improve HDL function in CKD is unknown.Design, setting, participants, & measurementsWe conducted a post hoc analysis of two randomized, clinical trials, IL-1 trap in participants with GFR 15–59 ml/min per 1.73 m2 (study A) and IL-1 receptor antagonist in participants on maintenance hemodialysis (study B), to evaluate if IL-1 blockade had improved the anti-inflammatory activity (IL-6, TNF-α, and Nod-like receptor protein 3), antioxidant function (superoxide production), and net cholesterol efflux capacity of HDL. HDL function was measured using LPS-stimulated THP-1 macrophages or peritoneal macrophages of apoE-deficient mice exposed to the apoB-depleted, HDL-containing fraction obtained from the plasma of the study participants, collected before and after the interventions to block IL-1 effects. Analysis of covariance was used for between group comparisons.ResultsThe mean age of the participants was 60±13 years, 72% (n=33) were men, and 39% (n=18) were black. There were 32 CKD (16 IL-1 trap and 16 placebo) and 14 maintenance hemodialysis (7 IL-1 receptor antagonist and 7 placebo) participants. Compared with placebo, IL-1 inhibition, in study A and B reduced cellular expression of TNF-α by 15% (P=0.05) and 64% (P=0.02), IL-6 by 38% (P=0.004) and 56% (P=0.08), and Nod-like receptor protein 3 by 16% (P=0.01) and 25% (P=0.02), respectively. The intervention blunted superoxide production in the treated arm compared with placebo, with the values being higher by 17% in the placebo arm in study A (P<0.001) and 12% in the placebo arm in study B (P=0.004). Net cholesterol efflux capacity was not affected by either intervention.ConclusionsIL-1 blockade improves the anti-inflammatory and antioxidative properties of the HDL-containing fraction of plasma in patients with stages 3–5 CKD, including those on maintenance hemodialysis.

scholarly journals HDL functions and their interaction in patients with ST Elevation Myocardial Infarction: a case control study

2020 ◽  
Author(s):  
Himani Thakkar ◽  
Vinnyfred Vincent ◽  
Ambuj Roy ◽  
Sandeep Singh ◽  
Lakshmy Ramakrishnan ◽  
...  
Keyword(s):  
Acute Phase ◽  
Cholesterol Efflux ◽  
Hdl Cholesterol ◽  
Pon1 Activity ◽  
Cholesterol Efflux Capacity ◽  
Coronary Syndrome ◽  
Hdl Function ◽  
Apolipoprotein A ◽  
The Mean

Abstract Background : Recent studies emphasize the importance of HDL function over HDL cholesterol measurement, as an important risk for cardiovascular diseases (CVD). We compared the HDL function of patients with Acute Coronary Syndrome (ACS) and healthy controls. Methods : We measured cholesterol efflux capacity of HDL using THP-1 macrophages labelled with fluorescently tagged (BODIPY) cholesterol. Paraoxonase and arylesterase activity of PON1 enzyme were assessed by spectrophotometric methods. Results : We recruited 151 ACS patients and 110 controls. The HDL function of all patients during acute phase and at six month follow-up was measured. The mean age of the patients and controls was 51.7 and 43.6 years respectively. The mean HDL cholesterol/apolipoprotein A-I levels (ratio) of patients during acute phase, follow-up and of controls were 40.2 mg/dl/ 112.5 mg/dl (ratio= 0.36), 38.3 mg/dl/ 127.2 mg/dl (ratio= 0.30) and 45.4 mg/dl/ 142.1 mg/dl (ratio=0.32) respectively. The cholesterol efflux capacity (CEC) of HDL was positively correlated with apolipoprotein A-I levels during acute phase (r = 0.19, p = 0.019), follow-up (r = 0.26, p = 0.007) and of controls (r = 0.3, p = 0.0012) but not with HDL-C levels (acute phase: r = 0.07, p = 0.47; follow-up: r = 0.1 , p = 0.2; control: r = 0.02, p = 0.82). Higher levels of cholesterol efflux capacity, PON1 activity and apolipoprotein A-I were associated with lower odds of development of ACS. We also observed that low CEC is associated with higher odds of having ACS if PON1 activity of HDL is also low and vice versa. Conclusion : ACS is associated with reduced HDL functions which improves at follow-up. The predicted probability of ACS depends upon individual HDL functions and the interactions between them.

scholarly journals Punicalagin Decreases Serum Glucose Levels and Increases PON1 Activity and HDL Anti-Inflammatory Values in Balb/c Mice Fed a High-Fat Diet

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Dana Atrahimovich ◽  
Abraham O. Samson ◽  
Ali Khattib ◽  
Jacob Vaya ◽  
Soliman Khatib
Keyword(s):  
Antioxidant Activity ◽  
High Fat Diet ◽  
Serum Proteins ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
High Fat ◽  
Glucose Levels ◽  
Hdl Function ◽  
Anti Inflammatory

Polyphenols are consumed daily in the human diet and are associated with reduced risk of a number of chronic diseases, including cancer, cardiovascular disease, and diabetes. Traditionally, the health benefits of polyphenols have been attributed to their antioxidant activity, but many studies might be hampered by oral administration and insignificant bioavailability. Rather than exerting a direct antioxidant effect, the mechanisms by which polyphenols express their beneficial effect seem to involve their interaction with proteins. The present study is aimed at broadening and confirming our recently published in vitro results showing that polyphenols may reduce atherosclerosis risk via interaction with proteins and lipoproteins related to atherosclerosis. The biological functions of punicalagin and quercetin in relation to glucose and lipid levels, paraoxonase 1 (PON1) activity, and inflammation were examined in vivo. Mice were fed a high-fat diet (HFD) for 12 weeks, and during the last 4 weeks, they received subcutaneous treatments via implanted minipumps, which released physiological concentrations of punicalagin, quercetin, or atorvastatin (as a positive control) daily into the serum. The HFD reduced serum PON1 activity, whereas punicalagin administration restored PON1 activity to the level of mice fed a normal diet. In addition, punicalagin significantly reduced glucose levels in HFD mice and improved HDL anti-inflammatory properties. In conclusion, beyond antioxidant activity, the mechanisms by which polyphenols exert their beneficial properties appear to involve their interaction with serum proteins that mediate HDL function and lipid-glucose state in the circulation.

scholarly journals HDL functions and their interaction in patients of ST Elevation MI Acute Coronary Syndrome: a case control study

2020 ◽  
Author(s):  
Himani Thakkar ◽  
Vinnyfred Vincent ◽  
Ambuj Roy ◽  
Sandeep Singh ◽  
Lakshmy Ramakrishnan ◽  
...  
Keyword(s):  
Acute Phase ◽  
Cholesterol Efflux ◽  
Hdl Cholesterol ◽  
Pon1 Activity ◽  
Cholesterol Efflux Capacity ◽  
Coronary Syndrome ◽  
Hdl Function ◽  
Apolipoprotein A ◽  
The Mean

Abstract Background: Recent studies emphasize the importance of HDL function over HDL cholesterol measurement, as an important risk for cardiovascular diseases (CVD). We compared the HDL function of patients with Acute Coronary Syndrome (ACS) and healthy controls.Methods: We measured cholesterol efflux capacity of HDL using THP-1 macrophages labelled with fluorescently tagged (BODIPY) cholesterol. Paraoxonase and arylesterase activity of PON1 enzyme were assessed by spectrophotometric methods. Results: We recruited 151 ACS patients and 110 controls. The HDL function of all patients during acute phase and at six month follow-up was measured. The mean age of the patients and controls was 51.7 and 43.6 years respectively. The mean HDL cholesterol/apolipoprotein A-I levels (ratio) of patients during acute phase, follow-up and of controls were 40.2 mg/dl/ 112.5 mg/dl (ratio= 0.36), 38.3 mg/dl/ 127.2 mg/dl (ratio= 0.30) and 45.4 mg/dl/ 142.1 mg/dl (ratio=0.32) respectively. The cholesterol efflux capacity (CEC) of HDL was positively correlated with apolipoprotein A-I levels during acute phase (r = 0.19, p = 0.019), follow-up (r = 0.26, p = 0.007) and of controls (r = 0.3, p = 0.0012) but not with HDL-C levels (acute phase: r = 0.07, p = 0.47; follow-up: r = 0.1 , p = 0.2; control: r = 0.02, p = 0.82). Higher levels of cholesterol efflux capacity, PON1 activity and apolipoprotein A-I were associated with lower odds of development of ACS. We also observed that low CEC is associated with higher odds of having ACS if PON1 activity of HDL is also low and vice versa. Conclusion: ACS is associated with reduced HDL functions which improves at follow-up. The predicted probability of ACS depends upon individual HDL functions and the interactions between them.

scholarly journals Cholesterol Efflux Capacity Associates with the Ankle-Brachial Index but Not All-Cause Mortality in Patients with Peripheral Artery Disease

Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1407
Author(s):  
Robert K. Clemens ◽  
Monika Hunjadi ◽  
Andreas Ritsch ◽  
Lucia Rohrer ◽  
Thomas O. Meier ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Cholesterol Efflux ◽  
Ankle Brachial Index ◽  
Mortality Rates ◽  
High Density Lipoproteins ◽  
Peripheral Artery ◽  
Cholesterol Efflux Capacity ◽  
Hdl Function ◽  
All Cause Mortality ◽  
Artery Disease

Background: Cholesterol efflux is an important mechanism by which high-density lipoproteins (HDLs) protect against cardiovascular disease. As peripheral artery disease (PAD) is associated with high mortality rates, mainly due to cardiovascular causes, we investigated whether cholesterol efflux capacity (CEC) of apolipoprotein B (apoB)-depleted plasma, a widely used surrogate of HDL function, may serve as a predictive marker for mortality in this patient population. Methods: In this prospective single-center study (median follow-up time: 9.3 years), apoB-containing lipoproteins were precipitated from plasma of 95 patients with PAD and incubated with J744-macrophages, which were loaded with radiolabeled cholesterol. CEC was defined as the fractional radiolabel released during 4 h of incubation. Results: Baseline CEC was lower in PAD patients that currently smoked (p = 0.015) and had a history of myocardial infarction (p = 0.011). Moreover, CEC showed a significant correlation with HDL-cholesterol (p = 0.003) and apolipoprotein A-I levels (p = 0.001) as well as the ankle-brachial index (ABI, p = 0.018). However, CEC did not differ between survivors and non-survivors. Neither revealed Kaplan–Meier and Cox regression analyses any significant association of CEC with all-cause mortality rates. Conclusion: Taken together, CEC is associated with ABI but does not predict all-cause mortality in patients with PAD.

Abstract 97: Increased Plasma Level of ApoCIII-rich Electronegative HDL May Contribute to Cognitive Impairment in Alzheimer’s Disease

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Hua-Chen Chan ◽  
Hsiao-Ting Lu ◽  
Mei-Chuan Chou ◽  
Ming-Hsien Tsai ◽  
Wei-Hsiang Chen ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cholesterol Efflux ◽  
Chemical Properties ◽  
Density Lipoprotein ◽  
Fold Increase ◽  
Anion Exchange Chromatography ◽  
Exchange Chromatography ◽  
Paraoxonase 1 ◽  
Cholesterol Efflux Capacity ◽  
Tnf Α

Background: High-density lipoprotein (HDL), the only lipoprotein class that can cross the blood brain barrier bidirectionally, is positively associated with cognitive functions. To delineate HDL’s role in Alzhenimer’s disease (AD), we analyzed the chemical properties of plasma HDL from AD and healthy normal adult (control) subjects. Methods and results: By using anion-exchange chromatography, we divided HDL into 5 increasingly electronegative subfractions, H1-H5. Compared to the control cohort (4.24±3.22%; n=20), HDL from AD patients (23.48±17.83%; n=30) had a 5.5-fold increase of H5 ( P <0.001; Figure ), accompanied by a decreased protein/lipid ratio attributed to a significant reduction of albumin essential for prevention of amyloid beta (Aβ) aggregation. As determined by LC/MS E and ProteinLynx Global SERVER (PLGS), AD-HDL was had a rich content of apolipoprotein (apo)CIII, but diminished amounts of sphingosine-1-phosphate (S1P)-associated apoM and antioxidative paraoxonase 1 (PON1). Exposure of murine RAW 264.7 macrophages to H5 induced vibrant expression of ganglioside GM1 in colocalization with apoCIII on lipid rafts, alongside a concomitant increase of TNF-α detectable in the cultured medium ( Figure ). LC/MS E examination localized posttranslational oxidation exclusively in ApoA1 residues of H5 in AD-HDL, which exhibited a compromised cholesterol efflux capacity. Conclusions: Plasma HDL from AD patients has a high proportion of H5, an apoCIII-rich electronegative HDL subfraction. The associated reduction in functional (albumin, S1P, apoM) and increase in proinflammatory (apoCIII, PON1, TNF-α) components may favor Aβ assembly and neuroinflammation. Additionally, a compromised cholesterol-efflux capacity of AD-HDL may also contribute to vascular cognitive impairment.

P3767Progressive left atrial remodeling associates with cholesterol efflux capacity of HDL in atrial fibrillation patients

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Takano ◽  
H Iwata ◽  
K Miyosawa ◽  
T Funamizu ◽  
H Hayashi ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Left Atrial ◽  
Cholesterol Efflux ◽  
Control Group ◽  
Atrial Remodeling ◽  
Inverse Association ◽  
Structural Remodeling ◽  
Cholesterol Efflux Capacity ◽  
Hdl Function

Abstract Background The clinical significance of high-density lipoprotein (HDL) function, represented by cholesterol efflux capacity (CEC), in addition to serum HDL cholesterol (HDL-C) levels, has been recognized in the pathogenesis and prognosis in patients with atherosclerotic cardiovascular diseases. However, the roles of HDL in the development and the progression of atrial fibrillation (AF), has been rarely evaluated. In this study, we thus hypothesized that the compromised HDL function may be associated with the progression of pathological structural remodeling in left atrium (LA). Objective We explored the association between CEC of HDL and the left atrial dimension (LAD), a maker of structural remodeling in the LA, in patients with AF and control. Methods This is a single center case-control study including consecutive 260 AF patients (AF group) and 34 paroxysmal supraventricular tachycardia (PSVT) patients (PSVT group, served as a control group), who underwent catheter ablation from July 2017 to December 2018. Blood samples were collected before catheter ablation procedure. CEC of HDL was measured by using ex vivo radiotracer system that involved incubation of [3H] cholesterol-loaded J774.1 murine macrophage-like cells with apoB-depleted serum. Results Serum HDL-C level was lower in AF group compared to those of PSVT group (55.3±15.3mg/dl vs 61.7±13.3mg/dl: p=0.024). As a marker of HDL function, CEC of HDL was significantly lower in patients with AF group compared to those in PSVT patients (4.74±0.84% vs 5.20±0.99%: p=0.005, Fig 1). In all patients including both groups, CEC of HDL was inversely correlated with LAD (r=−0.25; p<0.001, Fig 2), indicating the inverse association between HDL function and the progression of structural remodeling in AF. Moreover, multivariate logistic regression analysis adjusted by age, gender, body mass index, ejection fraction, and HDL-C demonstrated that increase in CEC of HDL was associated with the lower risk to be highest quartiles of LAD (>42mm), even adjusted by serum HDL-C levels (odds ratio of 1-SD elevation in CEC of HDL for LAD>42mm: 0.63; 95% confidence interval: 0.40–0.97, p=0.037), which implicated the link between HDL function and progression of left atrial structural remodeling. Conclusion Findings in this study may suggest that compromised HDL functionality is associated with the pathogenesis of left atrial structural remodeling in AF patients.

scholarly journals In Vivo Inflammation Does Not Impair ABCA1-Mediated Cholesterol Efflux Capacity of HDL

Cholesterol ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Remco Franssen ◽  
Alinda W. M. Schimmel ◽  
Sander I. van Leuven ◽  
Simone C. S. Wolfkamp ◽  
Erik S. G. Stroes ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Inflammatory Disease ◽  
Cholesterol Efflux ◽  
Chronic Inflammatory Disease ◽  
Cholesterol Efflux Capacity ◽  
Hdl Function ◽  
In Vivo Inflammation ◽  
The Impact

HDL provides atheroprotection by facilitating cholesterol efflex from lipid-laden macrophages in the vessel wall. In vitro studies have suggested impaired efflux capacity of HDL following inflammatory changes. We assessed the impact of acute severe sepsis and mild chronic inflammatory disease on the efflux capacity of HDL. We hypothesize that a more severe inflammatory state leads to stronger impaired cholesterol efflux capacity. Using lipid-laden THP1 cells and fibroblasts we were able to show that efflux capacity of HDL from both patients with severe sepsis or with Crohn's disease (active or in remission), either isolated using density gradient ultracentrifugation or using apoB precipitation, was not impaired. Yet plasma levels of HDL cholesterol and apoA-I were markedly lower in patients with sepsis. Based on the current observations we conclude that inflammatory disease does not interfere with the capacity of HDL to mediate cholesterol efflux. Our findings do not lend support to the biological relevance of HDL function changes in vitro.

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