High-density Lipoprotein Function Research Articles

Multi-omics profiling in spinal muscular atrophy (SMA): investigating lipid and metabolic alterations through longitudinal CSF analysis of Nusinersen-treated patients.

Spinal muscular atrophy (SMA) is a rare neuromuscular disease caused by biallelic mutations in the SMN1 gene, leading to progressive muscle weakness due to degeneration of the anterior horn cells. Since 2017, SMA patients can be treated with the anti-sense oligonucleotide Nusinersen, which promotes alternative splicing of the SMN2 gene, by regular intrathecal injections. In this prospective study, we applied metabolomic, lipidomic, and proteomic analysis to examine sequential CSF samples from 13 SMA patients and controls. This multi-omic approach identified over 800 proteins and 400 small molecules including lipids. Multivariate analysis of multi-omic data successfully discriminated between the CSF derived from SMA patients and control subjects. Lipidomic analysis revealed increased levels of cholesteryl esters and lyso-phospholipids, along with reduced levels of cholesterol and phospholipids in the CSF of SMA patients as compared to healthy controls. These data, combined with results from functional assays, led us to conclude that SMA patients exhibit altered levels and function of high-density-lipoprotein (HDL)-like particles in the CSF. Notably, Nusinersen therapy was observed to reverse disease-specific profile changes toward a physiological state, potentially explicable by restoring HDL function.

Reduced antioxidant high-density lipoprotein function in heart failure with preserved ejection fraction.

Heart failure (HF) is a heterogeneous clinical syndrome affecting a growing global population. Due to the high incidence of cardiovascular risk factors, a large proportion of the Western population is at risk for heart failure. Oxidative stress and inflammation play a crucial role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). While previous studies have demonstrated an association between dysfunctional HDL and heart failure, the specific link between oxidized HDL and HF remains unexplored. In this cross-sectional observational study, the antioxidant function of HDL was assessed in 366 patients with suspected heart failure. HFpEF assessment was conducted according to current guidelines. A validated cell-free biochemical assay was used to determine reduced HDL antioxidant function as assessed by increased HDL-lipid peroxide content (HDLox), normalized by HDL-C levels and the mean value of a pooled serum control from healthy participants (nHDLox; no units). Results were expressed as median with interquartile range (IQR). Participants with HFpEF (n = 88) had 15% higher mean relative levels of nHDLox than those without heart failure (n = 180). Using a basic multivariate model adjusted for age, sex, eGFR and a full multivariate model (adjusted for diabetes, hypertension, atrial fibrillation, LDL cholesterol, hsCRP, and coronary artery disease), nHDLox was an independent predictor for HFpEF (p < 0.05). An increase in 1-SD in nHDLox was associated with a 67% increased risk for HFpEF if compared with participants without heart failure (p = 0.02). HDL antioxidant function is reduced in patients with HFpEF. Improving HDL function is a promising target for early heart failure treatment.

The Role of Exercise-Based Cardiac Rehabilitation After Myocardial Infarction on Cholesterol Transfer to HDL.

High-density lipoprotein (HDL) is associated with decreased incidence of cardiovascular events, and its functionality also influences prognosis. Exercise is an important tool to improve prognosis in the post-infarction (MI) population, but the role of exercise on HDL functionality is poorly understood. Sixty-two patients with acute MI were randomized in a supervised exercise program for 12-14 weeks (exercise group-EG) or a control group (CG). The main objective of the study was to analyze the role of exercise on esterified cholesterol (EC) and unesterified cholesterol (UC) transfer to HDL. For the total population, the baseline mean rate of EC transfer to HDL was 2.53 ± 0.83 and at the end of follow-up, it was 2.74 ± 0.64 (p = 0.03). The figures for UC were, respectively, 4.08 ± 1.2 and 4.4 ± 1.06 (p = 0.02). The difference (follow-up minus baseline) for EC was 0.15 ± 0.84 for the control group and 0.27 ± 0.69 for the exercise group (p = 0.53); for UC, the figures were 0.28 ± 1.14 and 0.35 ± 0.96 (p = 0.80), respectively, for the control and exercise groups. In post-MI patients, 12-14 weeks of supervised exercise did not improve HDL functionality.

High-density lipoprotein alleviates ocular inflammation by downregulating M1 microglia and pyroptosis through regulating lipid accumulation and Caveolin-1 expression.

Uveitis encompasses a group of intraocular inflammatory diseases that are often associated with low levels of high-density lipoprotein (HDL). The role of HDL in intraocular inflammatory diseases remains unclear. In our research, we established an endotoxin-induced uveitis (EIU) model to investigate the role of HDL. Our study indicated that HDL could suppress ocular inflammation and restore retinal function in EIU mice. Specifically, HDL intervention effectively inhibited microglial activation and promoted the transformation of microglia from the M1 phenotype to the M2 phenotype. Furthermore, HDL intervention reduced microglial pyroptosis. Additionally, HDL was found to inhibit lipid accumulation in LPS-induced microglia, which is associated with inflammation, M1 polarization, and pyroptosis, by enhancing the expression of Caveolin-1 (CAV-1). Finally, we demonstrated that the function of HDL may be partially dependent on CAV-1 expression. We conclude that HDL inhibits pathological ocular inflammation by regulating M1/M2 phenotype polarization and pyroptosis through the modulation of lipid accumulation and CAV-1 expression. This suggests that HDL may represent a novel therapeutic strategy for ocular inflammation.

HDL-Free Cholesterol Influx into Macrophages and Transfer to LDL Correlate with HDL-Free Cholesterol Content

High-density lipoprotein (HDL)-free cholesterol (FC) transfers to other lipoproteins and cells, the former by a spontaneous mechanism and the latter by both spontaneous and receptor-mediated mechanisms. Macrophages are an important cell type in all stages of atherosclerotic cardiovascular disease (ASCVD), and the magnitude of FC efflux from macrophages to HDL, a metric of HDL function, inversely associates with several metrics of ASCVD. Very high plasma HDL concentrations are associated with increased all cause and ASCVD mortality, suggesting that the reverse process, FC influx from HDL into macrophages, is atherogenic. We hypothesize that HDL-FC is a metric of dysfunctional HDL, and when combined with HDL particle number (HDL-P), is an ASCVD risk factor. The magnitude of FC influx from HDL to macrophages is expected to be a function of HDL-P and HDL-FC content. Here we show that plasma HDL-FC content varies 2-fold among normolipidemic human subjects and linearly correlates with low-density lipoprotein (LDL)-FC content. The influx of HDL-FC into macrophages and transfer to LDL increase linearly with HDL-FC. As expected, influx of HDL-FC into macrophages and transfer to LDL are positively correlated. These data support the hypothesis that high HDL FC content is a marker for dysfunctional HDL, resulting in greater influx into macrophages and greater HDL-FC transfer to LDL. HDL-FC transfer to LDL is a valid surrogate for influx into macrophages. This study of HDL composition and function of normolipidemic subjects provides the basis for further investigation and establishment of HDL-FC content as an ASCVD risk factor.

Impact of metabolic-associated fatty liver disease on the cholesterol efflux capacity of high-density lipoproteins in adolescents with type 2 diabetes.

Type 2 diabetes (DM2) is an emerging disease in the pediatric population. DM2 is associated with metabolic-associated fatty liver disease (MAFLD). High-density lipoproteins (HDLs) are lipoproteins that are believed to have atheroprotective properties that reduce the risk of cardiovascular disease (CVD). Current evidence suggests that the physicochemical and functional features of HDLs may play a key role in the pathogenesis of atherosclerosis. We aimed to assess the impact of MAFLD on cholesterol efflux capacity (CEC) in adolescents with DM2. A cross-sectional study. Attention clinic for Children with Diabetes of the Hospital Infantil de México Federico Gómez. This study included a total of 70 adolescents, 47 of which had DM2 and 23 were healthy individuals. The presence of MAFLD was determined by MR spectroscopy with proton density fat fraction. We compared the distribution of HDL subtypes (HDL2b, HDL2a, HDL3a, HDL3b, and HDL3c) and the chemical composition of HDLs (total protein, triglycerides, phospholipids, cholesteryl esters, and free cholesterol). HDL functionality was determined by the CEC, measuring the fluorescent cholesterol efflux from J774 macrophage cells. We were expecting to observe a decrease in HDL efflux capacity in adolescents with type 2 diabetes and MAFLD. In our study, we observed a prevalence of MAFLD in 66% of adolescents with DM2, similar to that reported in other international studies (60%-80%). In the population with DM2 and MAFLD, we did not observe a decrease in CEC. Initially we found a slight elevation of CEC in adolescents with DM2, however, with the increase in liver fat, a little decrease is observed, which could explain a probable metabolic phenomenon, since the physicochemical composition and distribution of the particles is associated with the percentage of liver fat. A positive correlation between the percentage of liver fat and the concentration of HDL2b (p = 0.011), HDL2a (p = 0.014) and average particle size (p = 0.011) and the proportion of triglycerides inside the particles (p = 0.007). Likewise, negative correlation were found with the percentage of liver fat, cholesterol esters (p = 0.010) and free cholesterol of the particles (p < 0.001). We observed a positive correlation between CEC and the percentage of triglycerides (p = 0.007), and a negative correlation with the percentage of cholesterol esters (p = 0.05) inside the HDL's particles. In this group of adolescents with DM2, the presence of MAFLD was not associated with CEC; however, it is associated with abnormalities in the distribution and lipid composition of HDL particles. The momentum generated by the original proposal for MAFLD in the adult population and following the recommendations for pediatric MAFLD will be a step forward in helping to study the impact of MAFLD on the atheroprotective properties of HDL in the pediatric population.

Effect of Diet on HDL in Obesity.

Alterations of plasma lipoprotein levels and oxidative stress are frequently observed in obese patients, including low high-density lipoprotein (HDL) cholesterol (HDL-C) levels and alterations of HDL composition. Dysfunctional HDL with lower antioxidant and anti-inflammatory properties have also been demonstrated in obesity. There is increasing evidence that white adipose tissue (WAT) participates in several metabolic activities and modulates HDL-C levels and function. In obese subjects, the changes in morphology and function of adipose tissue lead to impaired regulatory function and are associated with a state of low-grade chronic inflammation, with increased release of pro-inflammatory adipokines and cytokines. These alterations may affect HDL metabolism and functions; thus, adipose tissue is considered a potential target for the prevention and treatment of obesity. A cornerstone of obesity prevention and therapy is lifestyle modification through dietary changes, which is reflected in the modulation of plasma lipoprotein metabolism. Some dietary components and metabolites directly affect the composition and structure of HDL and modulate its anti-inflammatory and vasoprotective properties. The aims of the review are to summarize the crosstalk between adipocytes and HDL dysfunction in human obesity and to highlight recent discoveries on beneficial dietary patterns as well as nutritional components on inflammation and HDL function in human obesity.

Single-nucleotide polymorphism rs670 in the promoter region of the apolipoprotein A-I gene

Apolipoprotein A-I (Apo A-I) plays a central role in the function of high-density lipoprotein (HDL). The rs670 single-nucleotide polymorphism (SNP) was identified as a cytosine-to-thymine (C&gt;T) transition in a cytosine&amp;ndash;phosphate&amp;ndash;guanine site within the promoter region of APOA1. Given its location, studies have hypothesized that this polymorphism may influence APOA1 expression, potentially impacting lipid and carbohydrate metabolism. The aim of this integrative review was to summarize all observational and experimental studies on the rs670 SNP available in the Scopus, ScienceDirect, dbSNP, and LitVar2 databases up to July 2024. In total, 162 articles were identified, of which 28 met the inclusion criteria. Most studies originated from Asia and were published between 2009 and 2023. Of the selected studies, 14 (50%) examined the association of the rs670 SNP with metabolic disorders. Among these, eight (28.57%) reported an association between the polymorphic allele and alterations in lipid profiles, proinflammatory markers, and insulin resistance. The remaining studies explored associations between the polymorphic allele and ischemic events, pharmacological therapies, diet, neurodegenerative diseases, pancreatitis, and breast cancer. The rs670 SNP occurs in more than 20% of the global population. Its position within the promoter region enables it to potentially regulate the APO cluster on chromosome 11. This review underscores the need for further investigation into the impact of this polymorphism on gene expression and its role in the pathogenesis of metabolic syndrome, cardiovascular disease, and cancer.

The role of high-density lipoproteins in sepsis.

High density lipoproteins (HDLs) are best known for their role in atherosclerotic cardiovascular diseases. However, efforts to reduce cardiovascular risk by increasing the concentration of cholesterol in HDL have failed, raising the question of whether HDL may have other, more central aspects to its role in health and disease. In epidemiological studies, low levels of HDL cholesterol are strongly associated with risk of infectious diseases and death from sepsis and, during sepsis, a larger decline in HDL cholesterol predicts a worse outcome. Many preclinical studies have examined strategies to augment HDL genetically or pharmacologically and have shown that this leads to protection from sepsis in animal models. Data in humans are more limited, but suggest a clinically relevant role of HDL in mediating the response to pathogen-associated lipids and preventing excessive inflammation. Collectively, these data raise the intriguing possibility that a clinically important biological function of HDL is as a component of the innate immune system and suggest that pharmacological manipulation of HDL may be a strategy to reduce the organ dysfunction and death that results from uncontrolled inflammation during sepsis. This review article discusses recent advances in our understanding of the role of HDL in sepsis.

HDL Cholesterol-Associated Shifts in the Expression of Preselected Genes Reveal both Pro-Atherogenic and Atheroprotective Effects of HDL in Coronary Artery Disease.

The associations of high-density lipoprotein (HDL) level and functionality with lipid metabolism, inflammation, and innate immunity in coronary artery disease (CAD) remain controversial. The differential expression of a set of genes related to HDL metabolism (24 genes) and atherogenesis (41 genes) in peripheral blood mononuclear cells (PBMC) from CAD and control patients with varied HDL cholesterol (HDL-C) levels was compared. 76 male patients 40-60 years old with CAD diagnosed by angiography and 63 control patients were divided into three groups with low, normal (1.0-1.4 mM), and increased HDL-C levels. Transcript levels were measured by real-time PCR. The differentially expressed genes (DEGs) and associated metabolic pathways were analyzed for three groups, with prevalent CAD as an outcome. The common feature was the increased odds ratio values for liver X receptor (LXR) gene expression for three patient groups. CAD patients with low HDL-C possessed 24 DEGs with lower expression of genes involved in cholesterol efflux, and down-regulated SREBF1 and ABCG1 are suggested as gene signatures. CAD patients with normal HDL-C possessed nine DEGs with down-regulated ITGAM and ALB as gene signatures. CAD patients with increased HDL-C possessed 19 DEGs with down-regulated APOA1 and HMGCR as gene signatures. With gene expression signatures, one standard deviation higher average gene expressions were associated with 5.1-, 48.8-, and 38.9-fold fewer CAD cases for three patient groups. As HDL-C increased in CAD patients, the expression of ABCG1, CUBN, and HDLBP genes increased, while the expression of HMGCR and NPC2 genes, involved in cholesterol synthesis and trafficking, decreased. The expression of CD14, CD36, S100A8, S100A9, S100A12, TLR5, TLR8, and VEGFA genes, involved in angiogenesis and inflammation mainly via nuclear factor-κB (NF-κB), decreased. The increased accumulation of cholesteryl ester in PBMC from patients with low HDL-C was suggested. This assumption contrasts with the suggested accumulation of free cholesterol in PBMC from patients with increased HDL-C, concomitant with suppression of cholesterol synthesis and traffic to the plasma membrane, and with an inflammatory state controlled by depressed CD36-mediated and upregulated apoE-mediated immunometabolic signaling. Gene signatures may be used for the diagnosis, prognosis, and treatment of CAD in dependence on HDL-C levels.

Abstract 4138633: Infusion of human apolipoprotein A-I (CSL112) promotes several aspects of reverse cholesterol transport

Background: High-density lipoprotein (HDL)-cholesterol is inversely correlated with cardiovascular risk, but increasing its circulating concentration is insufficient to prevent adverse cardiovascular outcomes. Instead, the emerging paradigm is on increasing the function of HDL and its major protein constituent apolipoprotein A-I (apoA-I), to increase reverse cholesterol transport. Objective: To investigate the effect of apoA-I [human] (CSL112) infusion on HDL protein composition, and provide further insights into the mechanism of action of CSL112 administered post-acute myocardial infarction (AMI). Methods: A mass spectrometry (MS)-based proteomic approach was used to evaluate changes in HDL protein composition in patients (n=50) from the AEGIS-I (ApoA-I Event Reducing in Ischemic Syndromes I) study who received either placebo or CSL112 post AMI. HDL was immuno-isolated from patient plasma using anti-apoA-I antibodies. Cholesterol esterification rate (CER) was measured to determine lecithin-cholesterol acyl transferase (LCAT) activity. Cholesterol efflux capacity (CEC) and hepatocyte uptake were assessed using patient serum in ex vivo cell-based assays. Results: CSL112 induced extensive rearrangement of HDL proteins at 4 hours post-infusion. Levels of apolipoproteins A2, B, C, and E as well as the acute phase proteins serum amyloid A1 and A4 were significantly reduced. By contrast, apoA-I, apoM, and LCAT significantly increased. Elevated apoA-I and LCAT levels on HDL were associated with an increase in CEC, plasma HDL-C levels, and CER in CSL112-treated patients. Furthermore, enhanced CEC strongly correlated with cholesterol uptake by hepatic cells (r=0.95 p&lt;0.001). Conclusion: CSL112 altered HDL composition and increased HDL functionality by promoting multiple steps of the reverse cholesterol transport pathway.

Abstract 4137895: Serum High-density Lipoprotein-Associated Paraoxonase-1 Levels Predict Recurrent Cardiovascular Events after Stent Implantation in Patients with Stable Angina Pectoris

Background: Poor clinical outcomes for patients undergoing hemodialysis (HD) after drug-eluting stent (DES) implantation have been reported. High-density lipoprotein (HDL) cholesterol is well-established as a negative risk factor for coronary artery disease, and its anti-oxidant property has been attributed mainly to the HDL-bound enzyme paraoxonase-1 (PON-1). Myeloperoxidase (MPO), a pro-oxidant enzyme released from activated neutrophils, has been shown to alter the atheroprotective function of HDL to a dysfunctional form. The aim of this study was to investigate the relationship between plasma MPO and serum PON-1 levels after implantation of DES in patients with stable angina pectoris (SAP) with and without HD. Methods: Serum PON-1 concentrations and PON-arylesterase activity were measured in 183 patients with SAP after DES implantation (HD group, n=37; non-HD group, n=146) with a sandwich ELISA method. Cardiovascular events were defined as sudden cardiac death, fatal or non-fatal myocardial infarction, cerebral infarction and other non-fatal events including unstable angina pectoris or coronary revascularization. Results: Serum PON-1 concentrations and PON-arylesterase activity were significantly lower in the HD group than in the non-HD group (PON-1 concentrations, P&lt;0.0001; PON-arylesterase activity, P&lt;0.0001). In addition, plasma MPO in patients undergoing HD were significantly higher than in patients not undergoing HD (P&lt;0.0001). Moreover, plasma MPO showed a significant inverse correlation with serum PON-1 concentrations and PON-arylesterase activity (concentration: R= -0.24, P=0.0013; arylesterase-activity: R=-0.24, P=0.0014). Cardiovascular event rates were significantly higher in the HD group than in the non-HD group (67.6% vs. 43.8%, P&lt;0.01). Kaplan-Meier survival analysis showed that the low-PON-1 group (&lt;58.0 mg/mL, median) had a significantly worse outcome than the high-PON-1 group ( P =0.013). Multivariate analysis showed that a low serum PON-1 concentration was the only independent predictor of cardiovascular events (odds ratio, 1.93; 95% confidence interval, 1.10 to 3.40, P =0.024). Conclusions: These findings demonstrate that plasma MPO have a significant inverse correlation with PON-1 in patients undergoing HD and suggest that an imbalance between pro-oxidants and anti-oxidants may contribute to the progression and destabilization of human coronary atherosclerotic lesions in patients with SAP who undergo HD following DES implantation.

ANGPTL3 as a target for treating lipid disorders in type 2 diabetes patients

Type 2 diabetes mellitus (T2DM) is a globally prevalent metabolic disorder, and cardiovascular disease (CVD) is a significant cause of mortality and morbidity in diabetic individuals. In addition to hyperglycemia, lipid abnormalities associated with T2DM play a crucial role in the development of CVD complications. Diabetic dyslipidemia is characterized by elevated levels of triglyceride (TG)-rich lipoproteins and small dense low-density lipoprotein (LDL) particles, reduced high-density lipoprotein (HDL) cholesterol, and impaired HDL function. Angiopoietin protein-like 3 (ANGPTL3) is a liver-derived protein that plays a crucial role in regulating plasma lipoprotein metabolism by inhibiting lipoprotein lipase and influencing lipid levels. Inhibiting ANGPTL3 has shown promising effects in promoting HDL-mediated cholesterol reverse transport and reducing the levels of TG-rich lipoproteins and LDL cholesterol. Here, we explore the potential of ANGPTL3 as a therapeutic target for lipid management in T2DM patients.

Impaired high-density lipoprotein-associated cholesterol efflux capacity predicts coronary rapid plaque progression

Abstract Background Rapid progression of coronary atherosclerotic plaques is recognized as a surrogate endpoint of cardiac ischemic events. Low high-density lipoprotein (HDL)-associated cholesterol efflux capacity (CEC) has been associated with atherosclerotic cardiovascular disease independent of HDL cholesterol (HDL-C) level. In this study, we aim to investigate the predictive role of CEC in rapid plaque progression (RPP). Methods We consecutively enrolled patients with stable angina from January 2017 to August 2019 in our hospital who underwent elective coronary angiography with at least one untreated coronary lesion. A follow-up angiography was performed at around 12 months. Afterwards, these patients were followed-up for every 3 months to June 2021. The primary endpoint was RPP during the 12-month angiography follow-up. The second endpoint was defined as a composite endpoint of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or unplanned coronary revascularization. Fluorescence-labeled cholesterol and J774 macrophages were used to measure CEC of ApoB-depleted serum samples. Results A total of 430 patients with 586 coronary lesions were included in the final analysis. During a mean follow-up of 12.7 ± 2.0 months, 120 lesions (20.5%) in 80 patients (18.6%) exhibited RPP. CEC, rather than HDL-C, was inversely associated with the extent of plaque progression (net luminal loss from the lowest to highest CEC quartile: 0.22±0.42 vs. 0.20±0.41 vs. 0.13±0.36 vs. 0.11±0.34 mm, P = 0.035). In multivariate analysis, baseline CEC was inversely associated with RPP independent of conventional risk and protective factors including HDL-C or apolipoprotein A-I. Subgroup analysis demonstrated that the association between CEC and RPP was more prominent in patients with high (≥4.02 mmol/L) than low (&amp;lt;4.02 mmol/L) total cholesterol. Finally, although patients with RPP had higher risk of the composite endpoint than those without RPP (P=0.012), no significant difference was observed between patients in different quartiles of CEC (P=0.720). Conclusions HDL-associated CEC is inversely associated with RPP in patients with coronary artery disease. HDL function assessment behaves as a better diagnostic biomarker than HDL-C for predicting RPP.

Favourable HDL composition in endurance athletes is not associated with changes in HDL in vitro antioxidant and endothelial anti-inflammatory function.

Given the failure of high-density lipoprotein (HDL) raising therapies to reduce cardiovascular disease risk, attention has turned towards HDL composition and vascular protective functions. In individuals with insulin resistance, exercise interventions recover HDL function. However, the effect of exercise on HDL in otherwise healthy individuals is unknown. This cross-sectional study aimed to measure HDL composition and antioxidant/endothelial anti-inflammatory function in insulin sensitive endurance athlete and healthy control men. HDL was isolated using density gradient ultracentrifugation. HDL composition was measured using microplate assays for apolipoprotein A-I, total cholesterol content and apolipoprotein M. HDL protein composition was measured using nano-liquid chromatography tandem mass spectrometry. HDL subclass distribution was measured by native gel electrophoresis. HDL in vitro antioxidant function was measured by paraoxonase-1 activity assay and anti-inflammatory function assessed in endothelial cells. Compared with controls, endurance athlete HDL had higher apolipoprotein A-1 (1.65 ± 0.62 mg/ml vs 1.21 ± 0.34 mg/ml, P=0.028) and higher total cholesterol content (2.09 ± 0.44 mmol/L vs 1.54 ± 0.33 mmol/L, P<0.001). Proteomics revealed higher apolipoprotein A-II, A-IV and D and transthyretin in endurance athlete HDL versus controls. There was no difference observed in in vitro HDL antioxidant or anti-inflammatory functions between controls and endurance athletes. Despite a more favourable composition, endurance athlete HDL did not have higher in vitro antioxidant or anti-inflammatory function. It is possible that HDL has a ceiling of function, i.e. that healthy HDL function cannot be enhanced by endurance exercise.

Associations Between High-Density Lipoprotein Cholesterol Efflux and Brain Grey Matter Volume.

Objective: High-density lipoprotein cholesterol efflux function may prevent brain amyloid beta deposition and neurodegeneration. However, the relevance of this finding has not been established in the diverse middle-aged population. Methods: We examined 1826 adults (47% Black adults) who participated in the Dallas Heart Study to determine associations between high-density lipoprotein (HDL) measures and brain structure and function. White matter hyperintensities (WMH) and whole-brain grey matter volume (GMV) were measured using brain MRI, and the Montreal Cognitive Assessment (MoCA) was used to measure neurocognitive function. HDL cholesterol efflux capacity (HDL-CEC) was assessed using fluorescence-labeled cholesterol efflux from J774 macrophages, and HDL particle size measures were assessed using nuclear magnetic resonance (NMR) spectroscopy (LipoScience). Multivariable linear regressions were performed to elucidate associations between HDL-CEC and brain and cognitive phenotypes after adjustment for traditional risk factors such as age, smoking status, time spent in daily physical activity, and education level. Results: Higher HDL-CEC and small HDL particle (HDL-P) concentration were positively associated with higher GMV normalized to total cranial volume (TCV) (GMV/TCV) after adjustment for relevant risk factors (β = 0.078 [95% CI: 0.029, 0.126], p = 0.002, and β = 0.063 [95% CI: 0.014, 0.111], p = 0.012, respectively). Conversely, there were no associations between HDL measures and WMH or MoCA (all p > 0.05). Associations of HDL-CEC and small HDL-P with GMV/TCV were not modified by ApoE-ε4 status or race/ethnicity. Interpretation: Higher HDL cholesterol efflux and higher plasma concentration of small HDL-P were associated with higher GMV/TCV. Additional studies are needed to explore the potential neuroprotective functions of HDL.

The Composition of the HDL Particle and Its Capacity to Remove Cellular Cholesterol Are Associated with a Reduced Risk of Developing Active Inflammatory Rheumatoid Arthritis.

In rheumatoid arthritis (RA), the risk of cardiovascular death is 50% higher compared to the general population. This increased risk is partly due to the systemic inflammation characteristic of RA and changes in the lipoprotein profiles. This study investigated plasma lipid levels, lipid ratios, and the composition and functionality of high-density lipoprotein (HDL) in control individuals and RA subjects based on the disease's inflammatory score (DAS28). This study included 50 control (CTR) individuals and 56 subjects with RA, divided into remission/low-activity disease (DAS28 < 3.2; n = 13) and active disease (DAS28 ≥ 3.2; n = 43). Plasma lipids (total cholesterol, TC; triglycerides, TG) and the HDL composition (TC; TG; phospholipids, PL) were determined using enzymatic methods; apolipoprotein B (apoB) and apoA-1 were measured by immunoturbidimetry. HDL-mediated cholesterol efflux and anti-inflammatory activity were assessed in bone marrow-derived macrophages. Comparisons were made using the Mann-Whitney test, and binary logistic regression was used to identify the predictors of active RA. A p-value < 0.05 was considered significant. TC, HDLc, and the TC/apoB ratio were higher in RA subjects compared to the CTR group. Subjects with active disease exhibited higher levels of TG and the TG/HDLc ratio and lower levels of HDLc, the TG/apoB ratio, TC, and apoA-1 in HDL particles compared to those with remission/low-activity RA. Increased levels of HDLc [odds ratio (OR) 0.931, 95% CI = 0.882-0.984], TC/apoB (OR 0.314, 95% CI = 0.126-0.78), HDL content in TC (OR 0.912, 95% CI = 0.853-0.976), PL (OR 0.973, 95% CI = 0.947-1.000), and apoA-1 (OR 0.932, 95% CI = 0.882-0.985) were associated with a decreased risk of active disease, but BMI (OR 1.169, 95% CI = 1.004-1.360) and TG (OR 1.031, 95% CI = 1.005-1.057) were positively associated with active disease. A reduction in HDL-mediated cholesterol efflux increased the OR for active RA by 26.2%. The plasma levels of HDLc, along with the composition and functionality of HDL, influence the inflammatory score in RA and may affect the development of cardiovascular disease.

High-density lipoprotein functionality in cholesterol efflux in early childhood is related to the content ratio of triglyceride to cholesterol

Cholesterol efflux capacity (CEC), commonly measured as a useful risk marker of atherosclerotic cardiovascular disease, depends on high-density lipoprotein (HDL) functionality and its concentration. We defined the relative HDL functionality in cholesterol efflux, not influenced by HDL concentration, as the ratio of measured CEC to standardized CEC (stCEC) based on HDL-cholesterol (HDL-C) of each individual using the curve regression equation obtained from the correlation. HDL-C, CEC, and CEC/stCEC levels in the < 28-day-old participants (neonates) were significantly low compared to those of the ≥ 28-day-old participants, indicating that the low CEC levels in the neonates depend on not only lower HDL-C but also lower HDL functionality. The low level of CEC/stCEC was remarkable in neonates born at < 34 weeks of gestation and did not improved to the reference level (1.000) until the infantile period. The relatively low or high CEC/stCEC ratios in neonates and infants were associated with lower or higher HDL-TG and HDL-TG/HDL-C ratio, respectively. However, no apparent effect of HDL-TG and HDL-TG/HDL-C ratio on CEC/stCEC was observed in the ≥ 1-year-old participants, indicating that HDL functionality in cholesterol efflux could be associated with the various HDL particles with various lipid compositions, but not just with HDL-TG and HDL-TG/HDL-C ratio.

Effect of a Multifactorial Weight Loss Intervention on HDL Cholesterol Efflux Capacity and Immunosenescence: A Randomized Controlled Trial

Objective Life expectancy and obesity prevalence are increasing worldwide, leading to an increase in the prevalence of cardiovascular disease. High-density lipoprotein (HDL) functionality and immunosenescence play key roles in cardiovascular disease, longevity, and quality of aging. Both molecular hallmarks of aging are impacted by obesity and metabolic syndrome and can be modulated by lifestyle. We aimed to evaluate the effect of a lifestyle intervention focused on an energy-reduced Mediterranean diet (erMedDiet), physical activity (PA), and behavioral support on HDL cholesterol efflux capacity (CEC) and immunosenescence. Method CEC and immunosenescent T cells were determined in 60 participants from the control group (CG) and 56 from the intervention group (IG) of the PREDIMED-Plus trial at baseline and after 1 and 3 years of follow-up. PREDIMED-Plus is a randomized, controlled, parallel-group trial with an IG of erMedDiet, PA promotion, and behavioral support for weight loss and a CG of usual primary care advice. The sample included 116 volunteers from the PREDIMED-Plus-IMDEA subsample of the PREDIMED-Plus trial. Men aged 55 to 75 years and women aged 60 to 75 years with a body mass index between 27 and 40 kg/m2 and metabolic syndrome were included. Results Participants within the IG had significantly improved CEC (2.42% and 10.69% after 1 and 3 years of follow-up) and a decreased in senescent T cell profile (−3.32% ± 12.54% and −6.74% ± 11.2%, p < 0.001, after 1 and 3 years of follow-up). Baseline obesity status impacted the response to the intervention. Conclusions A weight loss intervention program with erMedDiet and PA ameliorated senescence markers.

Decreased plasma in basal cell cancer

Aim Basal cell carcinoma (BCC) is one of the most common malignant non-melanoma carcinomas and is an important health problem for all countries. There are many studies on the effect of human lipoprotein metabolism and high-density lipoprotein (HDL-C) function on skin cells, but there are no detailed clinical studies on BCC yet. In addition, higher phospholipid and cholesterol content was found in cancerous and precancerous lesions of the skin compared to normal tissue. The aim of our study was to evaluate the lipid profile in patients with BCC and to try to find any relationship between BCC and molecules that have an important place in HDL-C functionality. Methods The patient group consisted of 39 patients who were clinically diagnosed with BCC by biopsy in hospital clinics. The control group (n:44) was randomly selected from patients of the same age group without a diagnosis of BCC who applied to different clinics of the same hospital. Routine lipid level, Apolipoprotein A1 (Apo-A1) level and Paraoxonase (PON- 1) enzyme measurements were made from serum samples taken from the patients and control groups participating in the study. Results The most important findings of this study, a statistically significant decrease in serum Apo-A1 level and a decrease trend in PON-1 enzyme can be considered in BCC patients compared to control groups. Conclusion Lipid metabolism and HDL functionality, may play a role in the development of BCC. Bangladesh Journal of Medical Science Vol. 23 No. 04 October’24 Page : 1060-1067