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.

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.

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 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.

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 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 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 Impaired HDL Metabolism Links GlycA, A Novel Inflammatory Marker, with Incident Cardiovascular Events

2019 ◽  
Vol 8 (12) ◽  
pp. 2137 ◽  
Author(s):  
Kayla A. Riggs ◽  
Parag H. Joshi ◽  
Amit Khera ◽  
Kavisha Singh ◽  
Oludamilola Akinmolayemi ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Inflammatory Marker ◽  
Coronary Revascularization ◽  
Hdl Cholesterol ◽  
High Sensitivity ◽  
High Density Lipoproteins ◽  
Acute Phase Reactants ◽  
Hdl Function ◽  
Hs Crp ◽  
The Impact

High-density lipoproteins (HDL) exert anti-atherosclerotic effects via reverse cholesterol transport, yet this salutary property is impaired in the setting of inflammation. GlycA, a novel integrated glycosylation marker of five acute phase reactants, is linked to cardiovascular (CV) events. We assessed the hypothesis that GlycA is associated with measures of impaired HDL function and that dysfunctional HDL may contribute to the association between GlycA and incident CV events. Baseline measurements of HDL cholesterol (HDL-C), HDL particle concentration (HDL-P), apoliprotein A1 (Apo A1), cholesterol efflux capacity, GlycA and high-sensitivity C-reactive protein (hs-CRP) were obtained from the Dallas Heart Study, a multi-ethnic cohort of 2643 adults (median 43 years old; 56% women, 50% black) without cardiovascular disease (CVD). GlycA was derived from nuclear magnetic resonance imaging. Participants were followed for first nonfatal MI, nonfatal stroke, coronary revascularization, or CV death over a median of 12.4 years (n = 197). The correlation between GlycA and hs-CRP was 0.58 (p < 0.0001). In multivariate models with HDL-C, GlycA was directly associated with HDL-P and Apo A1 and inversely associated with cholesterol efflux (standardized beta estimates: 0.08, 0.29, -0.06, respectively; all p ≤ 0.0004) GlycA was directly associated with incident CV events (adjusted hazard ratio (HR) for Q4 vs. Q1: 3.33, 95% confidence interval (CI) 1.99, 5.57). Adjustment for cholesterol efflux mildly attenuated this association (HR for Q4 vs. Q1: 3.00, 95% CI 1.75 to 5.13). In a multi-ethnic cohort, worsening inflammation, as reflected by higher GlycA levels, is associated with higher HDL-P and lower cholesterol efflux. Impaired cholesterol efflux likely explains some of the association between GlycA and incident CV events. Further studies are warranted to investigate the impact of inflammation on HDL function and CV disease.

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 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.

Environmental Factors Modifying HDL Functionality

2021 ◽  
Vol 28 ◽  
Author(s):  
Constantine E. Kosmas ◽  
Andreas Sourlas ◽  
Eliscer Guzman ◽  
Christina E. Kostara
Keyword(s):  
Environmental Factors ◽  
Cholesterol Efflux ◽  
Dietary Habits ◽  
Protein Composition ◽  
Hdl Cholesterol ◽  
Cardiovascular Effects ◽  
High Density Lipoproteins ◽  
Hdl Function ◽  
Hdl Functionality ◽  
The Impact

Background: Currently, it has been recognized that High-Density Lipoproteins (HDL) functionality plays a much more essential role in protection from atherosclerosis than circulating HDL-cholesterol (HDL-C) levels per se. Cholesterol efflux from macrophages to HDL, cholesterol efflux capacity (CEC) has been shown to be a key metric of HDL functionality. Thus, quantitative assessment of CEC may be an important tool for the evaluation of HDL functionality, as improvement of HDL function may lead to a reduction of the risk for Cardiovascular disease (CVD). Introduction: Although the cardioprotective action of HDLs is exerted mainly through their involvement in the reverse cholesterol transport (RCT) pathway, HDLs also have important anti-inflammatory, antioxidant, antiaggregatory and anticoagulant properties that contribute to their favorable cardiovascular effects. Certain genetic, pathophysiologic, disease states and environmental conditions may influence the cardioprotective effects of HDL either by inducing modifications in lipidome and/or protein composition or in the enzymes responsible for HDL metabolism. On the other hand, certain healthy habits or pharmacologic interventions may actually favorably affect HDL functionality. Method: The present review discusses the effects of environmental factors, including obesity, smoking, alcohol consumption, dietary habits, various pharmacologic interventions, as well as aerobic exercise, on HDL functionality. Result: Experimental and clinical studies or pharmacological interventions support the impact of these environmental factors in the modification of HDL functionality, although the mechanisms that are mediated are poorly understood. Conclusion: Further research should be conducted to unreal the underlying mechanisms of these environmental factors and to identify new pharmacologic interventions, capable of enhancing CEC, improving HDL functionality and potentially improving cardiovascular risk.

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