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 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 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.

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.

scholarly journals Impaired High‐Density Lipoprotein Function in Patients With Heart Failure

2021 ◽  
Author(s):  
Johanna E. Emmens ◽  
Congzhuo Jia ◽  
Leong L. Ng ◽  
Dirk J. van Veldhuisen ◽  
Kenneth Dickstein ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Cholesterol Concentration ◽  
Hdl Function ◽  
Patients With Heart Failure ◽  
Hdl Functionality ◽  
Anti Inflammatory

Background We recently showed that, in patients with heart failure, lower high‐density lipoprotein (HDL) cholesterol concentration was a strong predictor of death or hospitalization for heart failure. In a follow‐up study, we suggested that this association could be partly explained by HDL proteome composition. However, whether the emerging concept of HDL function contributes to the prognosis of patients with heart failure has not been addressed. Methods and Results We measured 3 key protective HDL function metrics, namely, cholesterol efflux, antioxidative capacity, and anti‐inflammatory capacity, at baseline and after 9 months in 446 randomly selected patients with heart failure from BIOSTAT‐CHF (A Systems Biology Study to Tailored Treatment in Chronic Heart Failure). Additionally, the relationship between HDL functionality and HDL proteome composition was determined in 86 patients with heart failure. From baseline to 9 months, HDL cholesterol concentrations were unchanged, but HDL cholesterol efflux and anti‐inflammatory capacity declined (both P <0.001). In contrast, antioxidative capacity increased ( P <0.001). Higher HDL cholesterol efflux was associated with lower mortality after adjusting for BIOSTAT‐CHF risk models and log HDL cholesterol (hazard ratio, 0.81; 95% CI, 0.71–0.92; P =0.001). Other functionality measures were not associated with outcome. Several HDL proteins correlated with HDL functionality, mainly with cholesterol efflux. Apolipoprotein A1 emerged as the main protein associated with all 3 HDL functionality measures. Conclusions Better HDL cholesterol efflux at baseline was associated with lower mortality during follow‐up, independent of HDL cholesterol. HDL cholesterol efflux and anti‐inflammatory capacity declined during follow‐up in patients with heart failure. Measures of HDL function may provide clinical information in addition to HDL cholesterol concentration in patients with heart failure.

scholarly journals Impaired high-density lipoprotein function in patients with heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J.E Emmens ◽  
J Congzhuo ◽  
L.L Ng ◽  
A.A Voors ◽  
R.A De Boer ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
Funding Source ◽  
Antioxidative Capacity ◽  
Hdl Function ◽  
Hdl Functionality ◽  
Anti Inflammatory ◽  
Over Time

Abstract Background We recently showed that a lower high-density lipoprotein cholesterol (HDL-C) concentration was one of the strongest predictors of death or heart failure (HF) hospitalisation in patients with HF. In a follow-up study, we suggested that this association could be partly explained by HDL proteome composition. However, whether the emerging concept of HDL function contributes to prognosis of HF patients has not been addressed. Methods We measured three key HDL function metrics, namely cholesterol efflux, antioxidative capacity, and anti-inflammatory capacity, at baseline and after 9 months in 446 randomly selected HF patients from BIOSTAT-CHF. Additionally, the relationship between HDL functionality and HDL proteome composition was determined in 86 patients. Results From baseline to 9 months, HDL-C concentrations did not substantially change, but HDL-mediated cholesterol efflux and anti-inflammatory capacity had decreased (both P&lt;0.001). In contrast, antioxidative capacity improved during the 9 months follow-up (P&lt;0.001). Higher HDL-mediated cholesterol efflux was independently associated with lower risk of mortality after adjustment for BIOSTAT risk models and log HDL-C (HR=0.81 [95% CI: 0.71–0.92], P=0.001). Other functionality parameters were not associated with outcome. Several HDL proteins correlated with HDL functionality, mainly with cholesterol efflux, and apolipoprotein A1 emerged as the main protein associated with all three functionality parameters. Conclusions HDL-mediated cholesterol efflux and anti-inflammatory capacity significantly decreased over time in patients with HF. Better baseline cholesterol efflux was prospectively associated with reduced mortality during follow-up independent of HDL-C. Combined these data indicate that HDL function measurements have the potential to provide clinical information beyond static HDL-C concentrations in HF patients. Changes in HDL functionality over time Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): European Commission

scholarly journals Serum cholesterol efflux capacity is associated with coronary plaque progression in patients with coronary heart disease

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
X Q Wang ◽  
S Feng ◽  
X Y Shu ◽  
C D Yang ◽  
R Y Zhang
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Coronary Angiography ◽  
Cholesterol Efflux ◽  
Hdl Cholesterol ◽  
Coronary Plaque ◽  
Plaque Progression ◽  
Cholesterol Efflux Capacity ◽  
Hdl Function

Abstract Background Coronary plaque progression is a major risk factor of adverse cardiac events in patients with coronary heart disease (CHD). Emerging evidence showed that attenuated high-density lipoprotein (HDL) function measured by cholesterol efflux capacity (CEC) was associated with development of atherosclerosis independent of HDL cholesterol level. In this study, we sought to investigate whether CEC is a predictor for coronary plaque progression in CHD patients. Methods We consecutively enrolled CHD patients from January 2017 to August 2019 in our Hospital who underwent elective percutaneous coronary intervention and had at least one non-target coronary lesion. Follow-up coronary angiography were performed at around 12 months. Fluorescence-labeled cholesterol and J774 macrophages were used to measure the CEC of ApoB-depleted serum sample from all patients. Quantitative coronary angiography (QCA) was performed both at baseline and follow-up to analyze the plaque progression. Results A total of 430 CHD patients with 586 non-target coronary lesions were included in the final analysis. During a mean follow-up time of 381.04±59.52 days, patients with decreased CEC presented more severe plaque progression (net luminal loss in highest to lowest CEC quartile: 0.22±0.42mm vs 0.20±0.41mm vs 0.13±0.36mm vs 0.11±0.34mm, p=0.035). In multivariate analysis, baseline CEC was independently associated with coronary plaque progression after adjustment for traditional risk factors including HDL cholesterol and ApoA-I, no matter treated as categorical variable (OR: 0.382 [95% CI 0.180–0.781] for highest to lowest quartile) or continuous variable (OR: 0.522 [95% CI 0.373–0.714] for per SD increase]. Furthermore, CEC demonstrated a better power in predicting coronary plaque progression compared with HDL cholesterol concentration (AUC=0.644 vs 0.514). Conclusions This study suggests that HDL function reflected by serum CEC is an independent predictor for coronary plaque progression in CHD patients. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation of China, Shanghai Municipal Commission of Health and Family Planning

Abstract P119: Changes in Cholesterol Efflux Capacity are Associated With Greater Progression of Aortic Calcification in Women at Midlife. Effects of Estradiol, Metabolic and Inflammatory Status

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Samar R El Khoudary ◽  
Jay Heinecke ◽  
Maria Brooks ◽  
Trevor Orchard ◽  
Patrick Hutchins ◽  
...  
Keyword(s):  
Median Time ◽  
Cholesterol Efflux ◽  
Time Difference ◽  
Aortic Calcification ◽  
Lipid Lowering ◽  
Time Varying ◽  
Mixed Effect ◽  
Cholesterol Efflux Capacity ◽  
Inflammatory Status ◽  
Hdl Function

Objective: High-density lipoprotein cholesterol efflux capacity (HDL-CEC) is associated inversely with CVD events. Recently, unexpected increases inHDL-CEC have been reported early after menopause. However, associations between HDL-CEC early changes and atherosclerotic progression in midlife women are not clear. We aimed to 1) test whether HDL-CEC changes from before to after menopause are associated with coronary (CAC) and aortic calcification (AC) progression anchored to the final menstrual period (FMP) date and 2) assess whether these associations could be explained by: time-varying estradiol, insulin resistance index (HOMA-IR), or C-reactive protein (CRP). Methods: Participants were fromthe Pittsburgh site of the Study of Women’s Health Across the Nation (SWAN). HDL-CEC and calibrated ion mobility HDL particles (HDL-Ps) were measured at two time points: one before and one after menopause (median time difference=6 Yr) and change in each metric was calculated as the difference between the two assessments. CAC and AC Agatston scores were available at the 2 nd time point (after menopause) and 2.08 Yr (median time difference) before that. Participants were not on lipid lowering medications or hormone therapy. Linear mixed effect models of repeated measures of log (AC+1) or log (CAC+1) as a function of within-woman change in HDL-CEC, race, time-varying BMI, time since 1 st calcification assessment and time before/after FMP were used. Progression of calcification per 1 year increase before/after FMP for every 1 unit increase in log HDL-CEC change were estimated by adding interaction between log HDL-CEC change and time before/after FMP to the above specified model. Estradiol, HOMA-IR, or CRP was added one at a time to the final models. Results: We studied 33 women (66 observations) (67% White and 33% Black) aged 52±2.3 Yr who were either peri- (64%) or postmenopause (36%) at calcification 1 st measure. At calcification 2 nd measure, all women were postmenopausal with a median time before/after FMP = 2.81 (Q1:1.84, Q3:4.30) Yr. Higher HDL-CEC change was associated with greater AC progression per 1 year increase before/after FMP (β(SE): 2.23(0.90) for every 1 log unit higher in HDL-CEC change, P =0.02). This association remained significant after adjusting for premenopausal HDL-CEC level, or changes in HDL-C or HDL-Ps. However, adjusting for estradiol, HOMA-IR, or CRP, the positive association between HDL-CEC and AC progression was largely attenuated and no longer significant. HDL-CEC changes were not associated with CAC progression. Conclusions: In this pilot study, increases in HDL-CEC early after menopause were associated with greater AC progression that was largely explained by midlife hormonal, metabolic or inflammation status. The midlife is a critical period that could impact HDL function and thus its cardio-protective effects. Our results should be retested in a larger setting.

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.

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