scholarly journals OX-HDL: A Starring Role in Cardiorenal Syndrome and the Effects of Heme Oxygenase-1 Intervention

Diagnostics ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 976
Author(s):  
Stephen J. Peterson ◽  
Abu Choudhary ◽  
Amardeep K. Kalsi ◽  
Shuyang Zhao ◽  
Ragin Alex ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Cardiorenal Syndrome ◽  
Renal Physiology ◽  
Heme Oxygenase 1 ◽  
Hdl Function ◽  
Hdl Dysfunction ◽  
Oxidative Processes ◽  
Pathway Regulation

In this review, we will evaluate how high-density lipoprotein (HDL) and the reverse cholesterol transport (RCT) pathway are critical for proper cardiovascular–renal physiology. We will begin by reviewing the basic concepts of HDL cholesterol synthesis and pathway regulation, followed by cardiorenal syndrome (CRS) pathophysiology. After explaining how the HDL and RCT pathways become dysfunctional through oxidative processes, we will elaborate on the potential role of HDL dysfunction in CRS. We will then present findings on how HDL function and the inducible antioxidant gene heme oxygenase-1 (HO-1) are interconnected and how induction of HO-1 is protective against HDL dysfunction and important for the proper functioning of the cardiovascular–renal system. This will substantiate the proposal of HO-1 as a novel therapeutic target to prevent HDL dysfunction and, consequently, cardiovascular disease, renal dysfunction, and the onset of CRS.

scholarly journals Interaction between adipocytes and high-density lipoprotein:new insights into the mechanism of obesity-induced dyslipidemia and atherosclerosis

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Tianhua Zhang ◽  
Jin Chen ◽  
Xiaoyu Tang ◽  
Qin Luo ◽  
Danyan Xu ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Adipose Tissue ◽  
Hormone Secretion ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
Atherosclerotic Cardiovascular Disease ◽  
Nutritional Disorder ◽  
Hdl Function ◽  
And Function

AbstractObesity is the most common nutritional disorder worldwide and is associated with dyslipidemia and atherosclerotic cardiovascular disease. The hallmark of dyslipidemia in obesity is low high density lipoprotein (HDL) cholesterol (HDL-C) levels. Moreover, the quality of HDL is also changed in the obese setting. However, there are still some disputes on the explanations for this phenomenon. There is increasing evidence that adipose tissue, as an energy storage tissue, participates in several metabolism activities, such as hormone secretion and cholesterol efflux. It can influence overall reverse cholesterol transport and plasma HDL-C level. In obesity individuals, the changes in morphology and function of adipose tissue affect plasma HDL-C levels and HDL function, thus, adipose tissue should be the main target for the treatment of HDL metabolism in obesity. In this review, we will summarize the cross-talk between adipocytes and HDL related to cardiovascular disease and focus on the new insights of the potential mechanism underlying obesity and HDL dysfunction.

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 High-density lipoprotein lipid peroxidation in association with presence of coronary artery disease and atrial fibrillation in a large cross-sectional study

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
N Pagonas ◽  
B Sasko ◽  
R Mueller ◽  
M Jaensch ◽  
W Dammermann ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Independent Predictor ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
Hdl Function ◽  
Antioxidant Function ◽  
Artery Disease

Abstract Background The function of high-density lipoprotein (HDL) cholesterol may play a more important role in the prevention of cardiovascular disease compared to the concentration of the HDL. Cardiovascular diseases such as coronary artery disease (CAD) and atrial fibrillation (AF) have been linked to impaired HDL function. Purpose The aim of the present study is to assess a biochemical measure of the antioxidant function of HDL and its association with presence of CAD and AF. Methods Patients admitted for elective cardiac catheterization were recruited in this cross-sectional study. Out of 1231 participants that were included in the analyses, 727 patients had confirmed CAD (CAD group), 369 patients had no CAD (no CAD group) and 129 persons were included as a control group. HDL function was measured in sera by determination of HDL-lipid peroxidation content (HDLox) assessed by a validated fluorometric cell-free biochemical assay and was normalized for the levels of HDL cholesterol (normalized HDLox/HDL-C ratio or nHDLox; no units). Results are expressed as median with interquartile range. Associations of nHDLox with presence of CAD and AF were assessed by univariate and multivariate analyses. Results Participants in the CAD group had higher levels of nHDLox (0.80, 0.61–1.03) compared to the no CAD (0.70, 0.55–0.93) and control (0.66, 0.55–1.03, no units, p&lt;0.001) group. Out of 1206 participants, 233 (19%) had AF and 973 (81%) had no AF. Patients with AF have also higher nHDLox (0.82, 0.60–10.03) compared to persons without AF (0.73, 0.58–0.98, p=0.03). In univariate analysis nHDLox was associated with CAD (p&lt;0.001). In multivariate analysis adjusted for age, gender, CAD, BMI and hypertension, nHDLox was a strong independent predictor of atrial fibrillation (p=0.015) but was not an independent predictor of CAD (p&gt;0.05) Conclusions Reduced antioxidant function of HDL (increased HDLox measured by a biochemical assay), a metric of HDL function, is increased in patients with atherosclerosis and manifested CAD and is also associated with the presence of atrial fibrillation independent of the presence of CAD. FUNDunding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Medical School of Brandenburg-MHB Fontane

Abstract 325: HDL Binding Rates for MPO: An Index of Functionality?

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Linghong Kong ◽  
Daisy Sahoo ◽  
Mary Sorci-Thomas ◽  
Hao Zhang ◽  
Kirkwood A Pritchard
Keyword(s):  
Metabolic Syndrome ◽  
Large Scale ◽  
Hypochlorous Acid ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Time Frame ◽  
Paraoxonase 1 ◽  
Hdl Function ◽  
Biophysical Interactions

Statement of Problem: Measurements of high density lipoprotein (HDL) function are reported to be more predictive for atheroprotection than measurements of HDL cholesterol. Unfortunately, bioassays of HDL function are complex, manual and time-consuming, making them impractical for routine clinical use. As such, well-standardized and easy-to-use assays of HDL function are desperately needed to make better informed clinical decisions. We are developing a panel of biolayer interferometry ( BLI ) assays on the Octet Red (forteBio, Inc) that measure HDL binding rates for biomolecules that regulate HDL function. Previously we showed that hypochlorous acid-modified HDL (ox-HDL) bound paraoxonase 1, myeloperoxidase (MPO) and cholesteryl ester transfer protein at faster rates than native HDL (n-HDL). Based on these data, we hypothesize that BLI assays of HDL binding rates might be useful for assessing functionality in vivo. Methods: To test this hypothesis, the biophysics of HDL interactions with MPO was examined in rodent models of metabolic syndrome and hypercholesterolemia and in patients with documented cardiovascular disease (CVD). Briefly, HDL was immunocaptured onto anti-apoA-I biosensors, incubated in a standardized solution of MPO and binding rates determined in ∼3.5 min/sample. Results: HDL from fructose-fed hamsters tended to bind MPO at faster rates than from chow-fed hamsters (300% of control p<0.07, n=6). HDL from hypercholesterolemic Ldlr -/- mice bound MPO at much faster rates than HDL from control mice (175% of control p<0.05, n=4). HDL from patients with CVD bound MPO at faster rates than HDL from control humans (280% of control p<0.004, n=6). Conclusions: HDL in hamsters with metabolic syndrome, mice with hypercholesterolemia and patients with CVD appears to bind MPO at faster rates than their corresponding controls. Automated BLI assays make it possible to complete large scale clinical studies in a reasonable time frame. Finally biophysical interactions of HDL with biomolecules such as MPO may be a useful approach for quantifying HDL functionality.

Az apolipoprotein M és a szfingozin-1-foszfát tengely jelentősége az érelmeszesedés kialakulásának gátlásában

2018 ◽  
Vol 159 (5) ◽  
pp. 168-175 ◽  
Author(s):  
Bíborka Nádró ◽  
Lilla Juhász ◽  
Anita Szentpéteri ◽  
Dénes Páll ◽  
György Paragh ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Vascular Inflammation ◽  
Critical Role ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Apolipoprotein M ◽  
Hdl Function ◽  
Atherosclerotic Process ◽  
And Migration ◽  
And Function

Abstract: Previous studies showed that plasma levels of high-density lipoprotein (HDL) cholesterol are inversely related to risk of cardiovascular diseases. However, in the last few decades it became obvious that beyond its plasma level, HDL structure and function have a critical role in its anti-atherogenic efficacy. Apolipoprotein M (ApoM) is an HDL-associated plasma protein affecting HDL metabolism and exhibits various anti-atherosclerotic functions, such as protection against oxidation and regulation of cholesterol efflux. Sphingosine 1-phosphate (S1P) is a potent sphingolipid mediator that regulates numerous cellular responses including cell differentiation and migration, apoptosis and vascular inflammation. The majority of S1P is associated to ApoM containing HDL particles. Therefore, ApoM and S1P content of HDL have an impact on the atherosclerotic process. Moreover, HDL-ApoM and S1P content can be altered in several pathologic conditions such as coronary artery disease. This review covers the currently available data on the contribution of ApoM and S1P to HDL function in health and cardiovascular diseases. Orv Hetil. 2018; 159(5): 168–175.

scholarly journals HDL Cholesterol Efflux Capacity is Impaired in Severe Short-Term Hypothyroidism Despite Increased HDL Cholesterol

2020 ◽  
Vol 105 (9) ◽  
pp. e3355-e3362
Author(s):  
Trynke van der Boom ◽  
Congzhuo Jia ◽  
Joop D Lefrandt ◽  
Margery A Connelly ◽  
Thera P Links ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Particle Concentration ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Antioxidative Capacity ◽  
Short Term ◽  
Cholesterol Efflux Capacity ◽  
Hdl Function ◽  
Particle Characteristics ◽  
The Impact

Abstract Context Severe hypothyroidism has profound effects on lipoprotein metabolism including high-density lipoprotein (HDL) cholesterol elevations but effects on HDL function metrics are unknown. Objective To determine the impact of severe short-term hypothyroidism on HDL particle characteristics, HDL cholesterol efflux capacity (CEC), and HDL antioxidative capacity. Design Observational study with variables measured during severe short-term hypothyroidism (median TSH 81 mU/L) and after 20 weeks of thyroid hormone supplementation (median TSH 0.03 mU/L) (Netherlands Trial Registry ID 7228). Setting University hospital setting in The Netherlands. Patients Seventeen patients who had undergone a total thyroidectomy for differentiated thyroid carcinoma. Main outcome measures HDL particle characteristics (nuclear magnetic resonance spectrometry), CEC (human THP-1-derived macrophage foam cells and apolipoprotein B-depleted plasma), and HDL anti-oxidative capacity (inhibition of low-density lipoprotein oxidation). Results During hypothyroidism plasma total cholesterol, HDL cholesterol and apolipoprotein A-I were increased (P ≤ 0.001). HDL particle concentration was unchanged, but there was a shift in HDL subclasses toward larger HDL particles (P &lt; 0.001). CEC was decreased (P = 0.035), also when corrected for HDL cholesterol (P &lt; 0.001) or HDL particle concentration (P = 0.011). HDL antioxidative capacity did not change. Conclusion During severe short-term hypothyroidism CEC, an important antiatherogenic metric of HDL function, is impaired. HDL cholesterol and larger HDL particles are increased but HDL particle concentration is unchanged. Combined, these findings suggest that HDL quality and quantity are not improved, reflecting dysfunctional HDL in hypothyroidism.

scholarly journals Prolonged bedrest reduces plasma high-density lipoprotein levels linked to markedly suppressed cholesterol efflux capacity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Athina Trakaki ◽  
Hubert Scharnagl ◽  
Markus Trieb ◽  
Michael Holzer ◽  
Helmut Hinghofer-Szalkay ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Oxidative Capacity ◽  
High Density ◽  
High Density Lipoproteins ◽  
Cholesterol Efflux Capacity ◽  
Vibration Exercise ◽  
Amyloid A ◽  
Hdl Function

Abstract Recent observations strongly connect high-density lipoproteins (HDL) function and levels with coronary heart disease outcomes and risk for infections and sepsis. To date, our knowledge of factors determining this connection is still very limited. The immobility associated with prolonged bedrest is detrimental to health, affecting several systems, including the cardiovascular, pulmonary, gastrointestinal, musculoskeletal and urinary. Effects of prolonged bedrest on the composition and functional properties of HDL remain elusive. We evaluated metrics of HDL composition and function in healthy male volunteers participating in a randomized, crossover head-down bedrest study. We observed that HDL cholesterol efflux capacity was profoundly decreased during bedrest, mediated by a bedrest associated reduction in plasma levels of HDL-cholesterol and major apolipoproteins (apo) apoA-I and apoA-II. Paraoxonase activity, plasma anti-oxidative capacity and the activities of lecithin-cholesterol acyltransferase and cholesteryl ester transfer protein were not affected. No change was observed in the content of HDL-associated serum amyloid A, a sensitive marker of inflammation. Resistive vibration exercise countermeasure during bedrest did not correct impaired cholesterol efflux capacity and only tended to increase arylesterase activity of HDL-associated paraoxonase. In conclusion, prolonged bedrest reduces plasma HDL levels linked to markedly suppressed HDL cholesterol efflux capacity. Resistive vibration exercise during bedrest did not correct HDL levels and impaired cholesterol efflux capacity.

scholarly journals Lower than average HDL cholesterol efflux capacity in Lithuanian population

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Sandra Kutkiene ◽  
Zaneta Petrulioniene ◽  
Dovile Karciauskaite ◽  
Aleksandras Laucevicius ◽  
Gabija Matuzevicienė ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Normal Weight ◽  
Abdominal Circumference ◽  
Control Group ◽  
Residual Cardiovascular Risk ◽  
Cross Sectional ◽  
Hdl Function ◽  
Lipid Panel

Abstract Background The aim of our study was to evaluate high-density lipoprotein cholesterol (HDL-C) efflux capacity in healthy controls and patients with severe dyslipidemia. Evaluation of HDL function may be beneficial for better understanding of cardiovascular diseases, as well as for taking actions to minimize residual cardiovascular risk. Methods During 2016–2017 a total of 93 participants – 48 (51.6%) women and 45 (48.4%) men – were included in this cross-sectional study. Data of 45 (48.4%) participants with severe dyslipidemia (SD) and 48 (51.6%) controls without dyslipidemia was used for statistical analysis. Total lipid panel, concentration of lipoprotein (a) and apolipoproteins were measured, data about cardiovascular risk factors were collected and detailed evaluation of HDL-C quality was performed for all patients. Results Increased HDL-C concentration was associated with higher ApoA1 (r = 0.866 in controls, r = 0.63 in SD group), ApoA2 (r = 0.41 in controls, r = 0.418 in SD group) and LDL-C concentrations (r = − 0.412 in SD group), lower ApoE (r = − 0.314 in SD group) and TG concentrations (r = − 0.38 in controls, r = − 0.608 in SD group), lower ApoB/ApoA1 ratio (r = − 0.567 in control group), below average HDL-C efflux capacity (r = − 0.335 in SD group), lower BMI (r = − 0.327 in controls, r = − 0.531 in SD group) and abdominal circumference (r = − 0.309 in women with SD). Below-average HDL-C efflux capacity was found in 67.7% (N = 63) of participants. It was more often found among patients with normal weight or BMI 30–31 kg/m2. HDL-C efflux capacity was inversely associated with HDL-C concentration (r = − 0.228). Conclusion Abnormal HDL function may be associated with residual cardiovascular risk in Lithuanian population.

scholarly journals HDL (High-Density Lipoprotein) Subclasses, Lipid Content, and Function Trajectories Across the Menopause Transition

2020 ◽  
Author(s):  
Samar R. El Khoudary ◽  
Xirun Chen ◽  
Alexis Nasr ◽  
Jeff Billheimer ◽  
Maria Mori Brooks ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Lipid Content ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
Menstrual Period ◽  
Resonance Spectroscopy ◽  
Hdl Function ◽  
Menopause Transition ◽  
And Function

Objective: The cardioprotective capacity of HDL (high-density lipoprotein) cholesterol postmenopause has been challenged. HDL subclasses, lipid contents, and function might be better predictors of cardiovascular risk than HDL cholesterol. Changes in these measures have not been characterized over the menopause transition (MT) with respect to timing relative to the final menstrual period. Approach and Results: Four hundred seventy-one women with HDL particle (HDL-P) subclasses (nuclear magnetic resonance spectroscopy total, large, medium, and small HDL-P and HDL size), HDL lipid content (HDL phospholipids and triglycerides), and HDL function (cholesterol efflux capacity [HDL-CEC]) measured for a maximum of 5 time points across the MT were included. HDL cholesterol and total HDL-P increased across the MT. Within the 1 to 2 years bracketing the final menstrual period, large HDL-P and HDL size declined while small HDL-P and HDL-triglyceride increased. Although overall HDL-CEC increased across the MT, HDL-CEC per HDL-P declined. Higher concentrations of total, large, and medium HDL-P and greater HDL size were associated with greater HDL-CEC while of small HDL-P were associated with lower HDL-CEC. Associations of large HDL-P and HDL size with HDL-CEC varied significantly across the MT such that higher large HDL-P concentrations and greater HDL size were associated with lower HDL-CEC within the 1 to 2 years around the final menstrual period. Conclusions: Although HDL cholesterol increased over the MT, HDL subclasses and lipid content showed adverse changes. While overall HDL-CEC increased, HDL-CEC per HDL-P declined, consistent with reduced function per particle. Large HDL-P may become less efficient in promoting HDL-CEC during the MT.

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