Metabolic syndrome (MS) is characterized by endothelial- and high-density lipoprotein (HDL) dysfunction and increased endothelial lipase (EL) serum levels. We examined the associations between EL serum levels, HDL (serum levels, lipid content, and function), and endothelial function in healthy volunteers (HV) and MS patients. Flow-mediated dilation (FMD), nitroglycerin-mediated dilation (NMD), serum levels of HDL subclasses (measured by nuclear magnetic resonance (NMR) spectroscopy), and EL serum levels differed significantly between HV and MS patients. The serum levels of triglycerides in large HDL particles were significantly positively correlated with FMD and NMD in HV, but not in MS patients. Cholesterol (C) and phospholipid (PL) contents of large HDL particles, calculated as HDL1-C/HDL1-apoA-I and HDL1-PL/HDL1-apoA-I, respectively, were significantly negatively correlated with FMD in HV, but not in MS patients. Cholesterol efflux capacity and arylesterase activity of HDL, as well as EL, were correlated with neither FMD nor NMD. EL was significantly negatively correlated with HDL-PL/HDL-apoA-I in HV, but not in MS patients, and with serum levels of small dense HDL containing apolipoprotein A-II in MS patients, but not in HV. We conclude that MS modulates the association between HDL and endothelial function, as well as between EL and HDL. HDL cholesterol efflux capacity and arylesterase activity, as well as EL serum levels, are not associated with endothelial function in HV or MS patients.

Endothelial lipase (EL) is a strong modulator of the high-density lipoprotein (HDL) structure, composition, and function. Here, we examined the impact of EL on HDL paraoxonase 1 (PON1) content and arylesterase (AE) activity in vitro and in vivo. The incubation of HDL with EL-overexpressing HepG2 cells decreased HDL size, PON1 content, and AE activity. The EL modification of HDL did not diminish the capacity of HDL to associate with PON1 when EL-modified HDL was incubated with PON1-overexpressing cells. The overexpression of EL in mice significantly decreased HDL serum levels but unexpectedly increased HDL PON1 content and HDL AE activity. Enzymatically inactive EL had no effect on the PON1 content of HDL in mice. In healthy subjects, EL serum levels were not significantly correlated with HDL levels. However, HDL PON1 content was positively associated with EL serum levels. The EL-induced changes in the HDL-lipid composition were not linked to the HDL PON1 content. We conclude that primarily, the interaction of enzymatically active EL with HDL, rather than EL-induced alterations in HDL size and composition, causes PON1 displacement from HDL in vitro. In vivo, the EL-mediated reduction of HDL serum levels and the consequently increased PON1-to-HDL ratio in serum increase HDL PON1 content and AE activity in mice. In humans, additional mechanisms appear to underlie the association of EL serum levels and HDL PON1 content.

The association between advanced oxidation protein products (AOPPs) and lipoprotein subclasses remains unexplored. Therefore, we performed comprehensive lipoprotein profiling of serum using NMR spectroscopy and examined the associations of lipoprotein subclasses with the serum levels of AOPPs in healthy volunteers (HVs) and patients with metabolic syndrome (MS). The serum levels of AOPPs were significantly positively correlated with the serum levels of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL); however, they were significantly negatively correlated with high-density lipoprotein (HDL). These lipoproteins (and their subclasses) differed markedly regarding the direction of correlations between their lipid contents and AOPPs. The strength of the correlations and the relative contributions of the subclasses to the correlations were different in the HVs and patients with MS. As revealed by orthogonal partial least squares discriminant analyses, the serum levels of IDL were strong determinants of AOPPs in the HVs, whereas the serum levels of VLDL and the lipid content of LDL were strong determinants in both groups. We conclude that IDL, VLDL, and LDL facilitate, whereas HDL diminishes the bioavailability of serum AOPPs. The presence of MS and the lipid contents of the subclasses affect the relationship between lipoproteins and AOPPs.

The association between serum levels of endothelial lipase (EL) and the serum levels and composition of apolipoprotein B (apoB)-containing lipoproteins in healthy subjects and patients with metabolic syndrome (MS) remained unexplored. Therefore, in the present study, we determined the serum levels and lipid content of apoB-containing lipoproteins using nuclear magnetic resonance (NMR) spectroscopy and examined their association with EL serum levels in healthy volunteers (HVs) and MS patients. EL was significantly negatively correlated with the serum levels of cholesterol in large very low-density lipoprotein (VLDL) particles, as well as with total-cholesterol-, free-cholesterol-, triglyceride-, and phospholipid-contents of VLDL and intermediate-density lipoprotein particles in MS patients but not in HVs. In contrast, EL serum levels were significantly positively correlated with the serum levels of apoB, triglycerides, and phospholipids in large low-density lipoprotein particles in HVs but not in MS patients. EL serum levels as well as the serum levels and lipid content of the majority of apoB-containing lipoprotein subclasses were markedly different in MS patients compared with HVs. We conclude that EL serum levels are associated with the serum levels and lipid content of apoB-containing lipoproteins and that these associations are markedly affected by MS.

Considering the relationship between disease severity and the extent of metabolic derangement in heart failure, we hypothesized that the serum levels of metabolites may have prognostic value for 1-year mortality in acute heart failure (AHF). The AHF study was a prospective, observational study enrolling consecutive patients hospitalized due to AHF. Metabolites were measured in serum collected at admission using NMR spectroscopy. Out of 315 AHF patients, 118 (37.5%) died within 1 year after hospitalization for AHF. The serum levels of 8 out of 49 identified metabolites were significantly different between patients who were alive and those who died within 1 year after hospitalization for AHF. Of these, only valine was significantly associated with 1-year mortality (hazard ratio 0.73 per 1 standard deviation increase, 95% confidence interval: 0.59–0.90, p = 0.003) in the multivariable Cox regression analyses. Kaplan–Maier analysis showed significantly higher survival rates in AHF patients with valine levels above the median (>279.2 µmol/L) compared to those with valine levels ≤ 279.2 µmol/L. In a receiver operating characteristics curve analysis, valine was able to discriminate between the two groups with an area under the curve of 0.65 (95% CI 0.59–0.72). We conclude that valine serum levels might be of prognostic value in AHF.

Acute heart failure (AHF) is associated with high short- and long-term mortality, and early identification of patients at highest risk remains challenging despite the use of established biomarkers and clinical risk scores. Oxidative stress plays a central role in the pathophysiology of AHF but has been insufficiently investigated as a prognostic target. This study aimed to evaluate the prognostic value of serum oxidative stress biomarkers for predicting short- and long-term mortality in AHF patients and to determine whether they improve risk stratification beyond established tools. Admission serum levels of malondialdehyde (MDA), advanced oxidation protein products (AOPPs), catalase, and superoxide dismutase (SOD) were measured in a cohort of 315 hospitalized AHF patients. Univariable and multivariable logistic regression analyses were performed to assess associations with in-hospital, 6-month, and 12-month mortality. Prognostic performance was compared with N-terminal pro-brain natriuretic peptide (NT-proBNP) and established risk scores (ADHERE, GWTG-HF, OPTIMIZE-HF) using receiver operating characteristics curves, the continuous net reclassification index (cNRI) and decision curve analysis. Serum MDA, catalase, and SOD were significantly elevated in non-survivors at all time points. In the adjusted analyses, MDA was the only oxidative stress marker independently associated with mortality. MDA showed robust prognostic performance, with improvements in AUC and cNRI as well as increased net benefit, when added to NT-proBNP or clinical scores. Survival analysis confirmed lower survival in patients with MDA ≥1.45 nmol/L (the median in our cohort). Other biomarkers (AOPPs, catalase, SOD) showed limited prognostic utility. Serum MDA is a robust, independent predictor of mortality in AHF. Incorporating MDA into routine assessment may enhance early identification of high-risk patients and support personalized management strategies in AHF.