Abstract 104: Serum from Patients with Aortic Valvular Stenosis Shows Decreased Cholesterol Efflux Capacities Despite Similar High-Density Lipoprotein Cholesterol Levels

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Benoit J Arsenault ◽  
Mathieu R Brodeur ◽  
David Rhainds ◽  
Anne-Elen Kernaleguen ◽  
Véronique Lavoie ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Pearson Correlation ◽  
Hdl Cholesterol ◽  
P Value ◽  
Aortic Valvular Stenosis ◽  
Cholesterol Efflux Capacity ◽  
Cholesterol Levels ◽  
Apolipoprotein A ◽  
Valvular Stenosis ◽  
Jet Velocity

Background: Studies have shown that low HDL-cholesterol levels may be associated with the progression of aortic valvular calcium and aortic valvular stenosis (AVS), but whether patients with AVS have impaired cholesterol efflux capacities is unknown. Methods and results: We have measured four parameters of cholesterol efflux capacity in apolipoprotein B-depleted serum samples from 48 patients with (aortic jet velocity ≥2.5 m/s, mean age = 72 ± 7 years and 72.7% men) and 51 patients without AVS (aortic jet velocity ≤ 1.7 m/s, mean age 71 ± 7 years and 70.6% men). Cholesterol efflux capacity was measured using J774 macrophages with and without stimulation of ABCA1 expression by cAMP (non-stimulated efflux, total efflux and ABCA1-mediated efflux), and HepG2 hepatocytes to measure SR-BI-mediated efflux. Mean HDL-cholesterol and apolipoprotein A-I levels as well as efflux are shown in the table for patients with vs. without AVS. The Pearson correlation coefficient between HDL-cholesterol levels and SR-B1-dependent efflux was 0.39 (p=0.007) in patients with AVS and 0.68 (<0.0001) in controls (P-value for the difference between the correlation coefficients obtained with Fisher’s test = 0.04). Conclusions: This study provides evidence that serum from patients with AVS may have impaired cholesterol efflux capacities, especially through the SR-B1 pathway. Table. Mean HDL-cholesterol and apolipoprotein A-I levels as well as non-stimulated-, total-, ABCA1-, and SR-B1-dependent cholesterol efflux obtained from patients’ serum with vs. without AVS. Data is shown as mean ± SD. Differences between categories were assessed using a Student unpaired t-test.

Abstract 17214: Differential Relationships Between Serum Cholesterol Efflux Capacities Measured From Three Cell Models and Coronary Artery Disease Status in the Montreal Heart Institute Biobank

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
David Rhainds ◽  
Low-Kam Cecile ◽  
Boulé Marie ◽  
Alem Sonia ◽  
Mongrain Ian ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Hdl Cholesterol ◽  
Disease Status ◽  
Cell Types ◽  
P Value ◽  
Montreal Heart Institute ◽  
Cholesterol Efflux Capacity ◽  
Heart Institute ◽  
Control Serum ◽  
The Difference

Recent clinical trials and Mendelian randomization studies suggest that raising HDL-cholesterol (HDL-C) concentration by itself is insufficient to lower cardiovascular (CV) risk, despite the established inverse relationship between HDL-C and cardiovascular risk. CV protection may derive from other characteristics of HDL. Such characteristics include the cholesterol efflux capacity of serum, the process by which HDL particles accept cholesterol from macrophages and other cell types. Recently, higher cholesterol efflux capacity was inversely associated with incident CV events over a >9 year period of follow-up, with a 67% risk reduction in the highest quartile of efflux. In our study, cholesterol efflux capacity was measured for 2000 patients from the Montreal Heart Institute Biobank as the ratio of pooled control serum. When comparing unadjusted cholesterol efflux values between 1000 controls and 1000 cases with previous myocardial infarction (MI), we observed significant decreases of efflux capacity in cases with J774 macrophages in basal and cAMP-stimulated conditions, with human HepG2 hepatocytes and with BHK cells expressing human ABCA1. In regression models of MI status against efflux variables, also adjusted for age, sex, HDL-C, triglycerides and statin use, the reduction in cholesterol efflux capacity in cases vs. controls remained highly significant for J774 cells in basal (p value = 5.8x10-11) and cAMP-stimulated conditions (p = 5.3x10-8), while the difference was lost with HepG2 cells (p=0.16) and was reversed for ABCA1-dependent efflux using BHK-ABCA1 cells (p=5.9x10-4). Thus, the relationship of cholesterol efflux capacity of serum HDL and cardiovascular status is heterogeneous, which suggest that the repertoire of cholesterol transporters expressed in cells and samples characteristics, such as the HDL proteome and lipidome, interact in a unique manner for each cell type. Future work will consist in identifying sources of such differences at the molecular level.

scholarly journals A loss-of-function variant in OSBPL1A predisposes to low plasma HDL cholesterol levels and impaired cholesterol efflux capacity

2016 ◽  
Vol 249 ◽  
pp. 140-147 ◽  
Author(s):  
Mahdi M. Motazacker ◽  
Juho Pirhonen ◽  
Julian C. van Capelleveen ◽  
Marion Weber-Boyvat ◽  
Jan Albert Kuivenhoven ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Hdl Cholesterol ◽  
Loss Of Function ◽  
Cholesterol Efflux Capacity ◽  
Cholesterol Levels

scholarly journals A loss-of-function variant in OSBPL1A predisposes to low plasma HDL cholesterol levels and impaired cholesterol efflux capacity

2016 ◽  
Vol 252 ◽  
pp. e259-e260
Author(s):  
J. van Capelleveen ◽  
J. Pirhonen ◽  
M.M. Motazacker ◽  
M. Weber-Boyvat ◽  
M. Jauhiainen ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Hdl Cholesterol ◽  
Loss Of Function ◽  
Cholesterol Efflux Capacity ◽  
Cholesterol Levels

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 Dysfunctional High-Density Lipoproteins Are Associated With a Greater Incidence of Acute Coronary Syndrome in a Population at High Cardiovascular Risk

Circulation ◽  
2020 ◽  
Vol 141 (6) ◽  
pp. 444-453 ◽  
Author(s):  
María Trinidad Soria-Florido ◽  
Olga Castañer ◽  
Camille Lassale ◽  
Ramon Estruch ◽  
Jordi Salas-Salvadó ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Cardiovascular Risk ◽  
Cholesterol Efflux ◽  
Hdl Cholesterol ◽  
Functional Characteristics ◽  
Cholesterol Efflux Capacity ◽  
Inflammatory Index ◽  
Coronary Syndrome ◽  
Apolipoprotein A ◽  
Sphingosine 1 Phosphate

Background: Studies have failed to establish a clear link between high-density lipoprotein (HDL) cholesterol and cardiovascular disease, leading to the hypothesis that the atheroprotective role of HDL lies in its biological activity rather than in its cholesterol content. However, to date, the association between HDL functional characteristics and acute coronary syndrome has not been investigated comprehensively. Methods: We conducted a case-control study nested within the PREDIMED (Prevención con Dieta Mediterránea) cohort, originally a randomized trial in which participants followed a Mediterranean or low-fat diet. Incident acute coronary syndrome cases (N=167) were individually matched (1:2) to control patients by sex, age, intervention group, body mass index, and follow-up time. We investigated 2 individual manifestations (myocardial infarction, unstable angina) as secondary outcomes. We measured the following functional characteristics: HDL cholesterol concentration (in plasma); cholesterol efflux capacity; antioxidant ability, measured by the HDL oxidative-inflammatory index; phospholipase A2 activity; and sphingosine-1-phosphate, apolipoproteins A-I and A-IV, serum amyloid A, and complement 3 protein (in apolipoprotein B–depleted plasma). We used conditional logistic regression models adjusted for HDL cholesterol levels and cardiovascular risk factors to estimate odds ratios (ORs) between 1-SD increments in HDL functional characteristics and clinical outcomes. Results: Low values of cholesterol efflux capacity (OR 1SD , 0.58; 95% CI, 0.40–0.83) and low levels of sphingosine-1-phosphate (OR 1SD , 0.70; 95% CI, 0.52–0.92) and apolipoprotein A-I (OR 1SD , 0.58; 95% CI, 0.42–0.79) were associated with higher odds of acute coronary syndrome. Higher HDL oxidative inflammatory index values were marginally linked to acute coronary syndrome risk (OR 1SD , 1.27; 95% CI, 0.99–1.63). Low values of cholesterol efflux capacity (OR 1SD , 0.33; 95% CI, 0.18–0.61), sphingosine-1-phosphate (OR 1SD : 0.60; 95% CI: 0.40–0.89), and apolipoprotein A-I (OR 1SD , 0.59; 95% CI, 0.37–0.93) were particularly linked to myocardial infarction, whereas high HDL oxidative-inflammatory index values (OR 1SD , 1.53; 95% CI, 1.01–2.33) and low apolipoprotein A-I levels (OR 1SD , 0.52; 95% CI, 0.31–0.88) were associated with unstable angina. Conclusions: Low cholesterol efflux capacity values, pro-oxidant/proinflammatory HDL particles, and low HDL levels of sphingosine-1-phosphate and apolipoprotein A-I were associated with increased odds of acute coronary syndrome and its manifestations in individuals at high cardiovascular risk. Clinical Trial Registration: URL: https://www.controlled-trials.com/ISRCTN35739639 . Unique identifier: ISRCTN35739639.

Abstract 433: Liver Disease Alters HDL Metabolism and Function

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Markus Trieb ◽  
Angela Horvath ◽  
Vanessa Stadlbauer ◽  
Ulrike Taschler ◽  
Sanja Curcic ◽  
...  
Keyword(s):  
Gel Electrophoresis ◽  
Cholesterol Efflux ◽  
Hdl Cholesterol ◽  
Paraoxonase Activity ◽  
Cholesterol Efflux Capacity ◽  
Cholesterol Levels ◽  
Hdl Function ◽  
Cirrhotic Patients ◽  
Native Gel ◽  
Hdl Metabolism

Background/Aims: High-density lipoproteins (HDLs) are important endogenous inhibitors of inflammatory responses. Dysfunctional HDL might contribute to the serious complications experienced by patients with acute and chronic liver failure, but the effect of cirrhosis on several metrics of HDL function is not understood. Methods: We measured metrics of HDL function in an explorative cross sectional study of 59 patients with compensated cirrhosis, 21 patients with acutely decompensated cirrhosis and 20 healthy controls. HDL particle size was assessed using native gel electrophoresis. HDL cholesterol efflux potential was assessed using [ 3 H]-cholesterol labeled macrophages. Paraoxonase activity was determined by photometry using phenylacetate as substrate. Nuclear factor-κB activation in monocytes and cytokines were assessed by flow cytometry. Endothelial regenerative activity was determined using an electric cell-substrate impedance sensing system. Results: Sera of cirrhotic patients showed low HDL-cholesterol levels and profoundly suppressed activities of several serum enzymes involved in HDL maturation and metabolism. Native gel electrophoresis analyses revealed that cirrhotic HDL shifts toward the larger HDL 2 subclass. We observed that (i) HDL cholesterol efflux capability, (ii) paraoxonase activity, (iii) the ability to inhibit monocyte production of pro-inflammatory cytokines and (iv) endothelial regenerative activities were significantly reduced in stable cirrhotic patients, and markedly suppressed in acutely decompensated patients. Of particular interest, HDL cholesterol efflux capacity appeared to be strongly associated with mortality of cirrhotic patients, independently of HDL cholesterol levels. Conclusion: Cirrhosis affects HDL metabolism and several metrics of HDL function. HDL cholesterol efflux capacity appears to predict 1-year mortality independent of HDL-cholesterol levels.

Abstract 19753: Hdl Cholesterol Efflux Capacity is Inversely Associated With Incident Chd Events Independent of Hdl-c and Apoa-i Concentrations

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Danish Saleheen ◽  
Robert Scott ◽  
Sunda Javad ◽  
Wei Zhao ◽  
Amrith Rodrigues ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Ex Vivo ◽  
Control Sample ◽  
Hdl Cholesterol ◽  
P Value ◽  
Cholesterol Efflux Capacity ◽  
Hdl Function ◽  
Chd Risk ◽  
A Prospective Study ◽  
Nested Case Control

Background: Although plasma HDL-C levels are strongly associated with risk of coronary heart disease (CHD), interventions that raise HDL-C have not been shown to reduce CHD risk. A prototypical measure of HDL function, namely HDL cholesterol efflux capacity, has been shown to be associated with prevalent CHD even after adjusting for HDL-C, but its association with incident CHD events remains uncertain. Methods: We measured HDL cholesterol efflux capacity and assessed its relationship to incident CHD events in a nested case control sample within a prospective study (EPIC-Norfolk) of 25,639 individuals aged 40-79 years examined in 1993-1997 and followed up to 2009. We quantified efflux capacity in 1895 incident CHD cases and 2474 control participants free of any cardiovascular disorders, by using a validated ex-vivo radiotracer assay that involved incubation of J774 macrophages with apoB-depleted serum from the study participants. Results: HDL cholesterol efflux capacity was positively correlated with HDL-C levels (r2=0.27; P-value<5x10-5) and apoA-I (r2=0.24;P-value< 5x10-5). In analyses comparing top versus bottom third, cholesterol efflux capacity was significantly inversely associated with incident CHD, independent of age, sex, diabetes, hypertension, smoking and alcohol use, waist-to-hip ratio, BMI, LDL-C levels and even after controlling for HDL-C or apoA-I (OR: 0.75 [0.53, 0.97];P-value:9.1x10-3) (Figure). Conclusions: HDL cholesterol efflux capacity is significantly and inversely associated with incident CHD events, independent of established vascular risk factors and after adjusting for HDL-C and apoA-I levels.

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 High Density Lipoprotein Cholesterol Efflux Capacity and Atherosclerosis in Cardiovascular Disease: Pathophysiological Aspects and Pharmacological Perspectives

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 574
Author(s):  
Maria Pia Adorni ◽  
Nicoletta Ronda ◽  
Franco Bernini ◽  
Francesca Zimetti
Keyword(s):  
High Density Lipoprotein ◽  
Cholesterol Efflux ◽  
Current Knowledge ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
Current Evidence ◽  
Endocrine Disorders ◽  
Lifestyle Modifications ◽  
Cholesterol Efflux Capacity

Over the years, the relationship between high-density lipoprotein (HDL) and atherosclerosis, initially highlighted by the Framingham study, has been revealed to be extremely complex, due to the multiple HDL functions involved in atheroprotection. Among them, HDL cholesterol efflux capacity (CEC), the ability of HDL to promote cell cholesterol efflux from cells, has emerged as a better predictor of cardiovascular (CV) risk compared to merely plasma HDL-cholesterol (HDL-C) levels. HDL CEC is impaired in many genetic and pathological conditions associated to high CV risk such as dyslipidemia, chronic kidney disease, diabetes, inflammatory and autoimmune diseases, endocrine disorders, etc. The present review describes the current knowledge on HDL CEC modifications in these conditions, focusing on the most recent human studies and on genetic and pathophysiologic aspects. In addition, the most relevant strategies possibly modulating HDL CEC, including lifestyle modifications, as well as nutraceutical and pharmacological interventions, will be discussed. The objective of this review is to help understanding whether, from the current evidence, HDL CEC may be considered as a valid biomarker of CV risk and a potential pharmacological target for novel therapeutic approaches.

Sign in / Sign up

Export Citation Format

Share Document