Publications by authors named "Hubert Scharnagl"

Article Synopsis
  • ANGPTL3/4/8 proteins regulate lipoprotein lipase (LPL) activity, with ANGPTL8 forming complexes that influence ANGPTL4's function; however, their association with cardiovascular outcomes is under-researched.
  • This study involved measuring various ANGPTL proteins and complexes in two large population studies (LURIC and getABI) focusing on cardiovascular health and outcomes over several years.
  • Findings showed that while ANGPTL3/8 inhibited LPL activity and correlated with increased LDL-C and triglycerides, they did not predict cardiovascular death; however, ANGPTL4/8 and CD-ANGPTL4 were linked to higher diabetes prevalence and increased cardiovascular mortality risk.
View Article and Find Full Text PDF
Article Synopsis
  • This study examined the effects of inhibiting adipose triglyceride lipase (ATGL) on the progression of metabolic dysfunction-associated steatohepatitis (MASH) and related liver fibrosis in mice on a high-fat diet.
  • Mice treated with the ATGL inhibitor Atglistatin showed improvements in liver health, including lower liver enzymes and reduced lipid accumulation, revealing changes in gene expressions linked to liver and bile acid metabolism.
  • The findings suggest that ATGL inhibition disrupts PPARα signaling pathways and alters bile acid synthesis, which may provide a therapeutic target for treating liver diseases associated with metabolic dysfunction.
View Article and Find Full Text PDF

The strong associations between the serum levels of adiponectin and the lipoprotein subclasses observed in healthy subjects are much weaker in patients with metabolic syndrome (MS). However, the impact of sex on these associations remained unexplored. Therefore, in the present study, we examined associations between adiponectin and the lipoprotein subclasses, analyzed by nuclear magnetic resonance spectroscopy, separately in healthy females and males, as well as in females and males with MS.

View Article and Find Full Text PDF

Aims: Inflammation accompanies heart failure (HF) and elevated levels of inflammatory biomarkers are linked to new onset of HF. However, whether the prognostic relevance of inflammatory biomarkers is different in HF with reduced (HFrEF) and preserved ejection fraction (HFpEF) is unclear. The aim of the current study is to explore the role of inflammation on the mortality risk in patients with HF.

View Article and Find Full Text PDF

Objectives: The role of vitamin D deficiency in cardiovascular disease (CVD) is controversial. Inherent biological and analytical limitations compromise the specificity of widely used 25-hydroxyvitamin D [25(OH)D] cut-offs. Simultaneous determination of 25(OH)D and 24,25-dihydroxyvitamin D [24,25(OH)D] permits a functional assessment of vitamin D metabolism.

View Article and Find Full Text PDF

Metabolic syndrome (MS) is a widespread disease in developed countries, accompanied, among others, by decreased adiponectin serum levels and perturbed lipoprotein metabolism. The associations between the serum levels of adiponectin and lipoproteins have been extensively studied in the past under healthy conditions, yet it remains unexplored whether the observed associations also exist in patients with MS. Therefore, in the present study, we analyzed the serum levels of lipoprotein subclasses using nuclear magnetic resonance spectroscopy and examined their associations with the serum levels of adiponectin in patients with MS in comparison with healthy volunteers (HVs).

View Article and Find Full Text PDF

Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have been suggested to exert cardioprotective effects in patients with heart failure, possibly by improving the metabolism of ketone bodies in the myocardium.

Methods: This post hoc analysis of the EMMY trial investigated the changes in serum β-hydroxybutyrate (3-βOHB) levels after acute myocardial infarction (AMI) in response to 26-week of Empagliflozin therapy compared to the usual post-MI treatment. In addition, the association of baseline and repeated measurements of 3-βOHB with cardiac parameters and the interaction effects of Empagliflozin were investigated.

View Article and Find Full Text PDF
Article Synopsis
  • PCSK9 is important in lipid metabolism, with higher levels in women throughout their lives, and statin treatment influences these levels with potential genetic variances affecting results by sex.* -
  • The study involved meta-analyses of PCSK9 levels in over 14,000 individuals, analyzing the effects of both sex and statin treatment on genetic associations related to PCSK9 and LDL cholesterol levels.* -
  • Results highlighted 11 genetic loci linked to PCSK9, with some showing different effects based on sex and statin status, including novel associations for specific groups; this suggests distinct genetic influences on cholesterol levels based on gender and medication use.*
View Article and Find Full Text PDF

Aims: To investigate the prevalence of familial hypercholesterolaemia (FH) and compare the performance of clinical criteria and genetic testing in patients undergoing coronary angiography.

Methods And Results: The prevalence of FH was determined with the Dutch Lipid Clinical Network (DLCN), US 'Make Early Diagnosis to Prevent Early Death' (US-MEDPED), Simon Broome (SB) criteria, the 'familial hypercholesterolaemia case ascertainment tool' (FAMCAT), and a clinical algorithm. Genetic screening was conducted with a custom array from Affymetrix (CARRENAL array) harbouring 944 FH mutations.

View Article and Find Full Text PDF
Article Synopsis
  • Lipoprotein(a) (Lp(a)) is a genetically determined risk factor for cardiovascular diseases, and its levels can vary widely among individuals.
  • A study on 86 patients post-ST elevation myocardial infarction found that Lp(a) levels increased significantly from hospital admission to a 3 to 6 month follow-up, indicating a changing response after the event.
  • The research suggests that monitoring Lp(a) levels after a myocardial infarction is important for assessing individual treatment needs based on specific Lp(a) cut-off levels.
View Article and Find Full Text PDF

Clinically, disorders of lipid metabolism often remain without symptoms. Typical skin lesions, however, can be indicative. Secondary hyperlipoproteinemias (HLP) are more common than primary hyperlipoproteinemias; they can (partially) be improved by treating the underlying disease.

View Article and Find Full Text PDF

Background & Aims: The nuclear receptor farnesoid X receptor (FXR) is a key regulator of hepatic bile acid (BA) and lipid metabolism, inflammation and fibrosis. Here, we aimed to explore the potential of cilofexor (GS-9674), a non-steroidal FXR agonist, as a therapeutic approach for counteracting features of cholestatic liver injury by evaluating its efficacy and mechanisms in the knockout () mouse model of sclerosing cholangitis.

Methods: FVB/N wild-type and or BALB/c wild-type and mice were treated with 0, 10, 30 or 90 mg/kg cilofexor by gavage every 24 h for 10 weeks.

View Article and Find Full Text PDF

Background: Determining serum 25-hydroxyvitamin D [25(OH)D], 24,25-dihydroxyvitamin D [24,25(OH)2D] and the vitamin D metabolite ratio (VMR) allows the identification of individuals with a low vitamin D metabolite profile. Here, we evaluated if such a functional approach provides superior diagnostic information to serum 25(OH)D alone.

Methods: 25(OH)D, 24,25(OH)2D, and the VMR were determined in participants of the DESIRE (Desirable Vitamin D Concentrations, n = 2010) and the LURIC (Ludwigshafen Risk and Cardiovascular Health, n = 2456) studies.

View Article and Find Full Text PDF

Background And Aims: Schistosoma mansoni infection is one of the worldwide leading causes of liver fibrosis and portal hypertension. The objective of this study was to evaluate whether polyhydroxylated bile acids (BAs), known to protect mice from the development of acquired cholestatic liver injury, counteract S. mansoni-induced inflammation and fibrosis.

View Article and Find Full Text PDF

Background & Aims: Glucagon-like peptide (GLP)-2 may exert antifibrotic effects on hepatic stellate cells (HSCs). Thus, we aimed to test whether application of the GLP-2 analogue teduglutide has hepatoprotective and antifibrotic effects in the Mdr2/Abcb4 mouse model of sclerosing cholangitis displaying hepatic inflammation and fibrosis.

Methods: Mdr2 mice were injected daily for 4 weeks with teduglutide followed by gene expression profiling (bulk liver; isolated HSCs) and immunohistochemistry.

View Article and Find Full Text PDF

Aims: Apolipoprotein C-II (ApoC-II) is thought to activate lipoprotein lipase (LPL) and is therefore a possible target for treating hypertriglyceridemia. Its relationship with cardiovascular risk has not been investigated in large-scale epidemiologic studies, particularly allowing for apolipoprotein C-III (ApoC-III), an LPL antagonist. Furthermore, the exact mechanism of ApoC-II-mediated LPL activation is unclear.

View Article and Find Full Text PDF

Preeclampsia (PE) is linked to an overall increased cardiovascular risk for both the mother and child. Functional impairment of high-density lipoproteins (HDL) may contribute to the excess cardiovascular risk associated with PE. In this study, we investigated the effects of PE on maternal and neonatal lipid metabolism, and the parameters of HDL composition and function.

View Article and Find Full Text PDF

Objective: In this study, we aimed to establish the causal effects of lowering sclerostin, target of the antiosteoporosis drug romosozumab, on atherosclerosis and its risk factors.

Methods: A genome-wide association study meta-analysis was performed of circulating sclerostin levels in 33,961 European individuals. Mendelian randomization (MR) was used to predict the causal effects of sclerostin lowering on 15 atherosclerosis-related diseases and risk factors.

View Article and Find Full Text PDF

Branched-chain amino acids (BCAAs) are effectors of metabolic diseases, but their impact on mortality is largely unknown. We investigated the association of BCAA with risk factors and mortality in 2,236 participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study using linear and Cox regression. Adiponectin, hemoglobin, C-peptide, hemoglobin A, and homoarginine showed the strongest association with BCAA concentration (all p < 0.

View Article and Find Full Text PDF
Article Synopsis
  • * A working group aims to create a standardized reference measurement system for Lp(a) that uses mass spectrometry and certified reference materials for accurate assessment.
  • * The study found that unspiked human serum pools work well as secondary reference materials, while spiked serum pools showed inconsistencies when compared to clinical samples.
View Article and Find Full Text PDF

The HDL proteome has been widely recognized as an important mediator of HDL function. While a variety of HDL isolation methods exist, their impact on the HDL proteome and its associated function remain largely unknown. Here, we compared three of the most common methods for HDL isolation, namely immunoaffinity (IA), density gradient ultracentrifugation (UC), and dextran-sulfate precipitation (DS), in terms of their effects on the HDL proteome and associated functionalities.

View Article and Find Full Text PDF

Background: Impaired renal function is associated with cardiovascular and all-cause mortality. In the general population, HDL-cholesterol is associated with cardiovascular events, which is not true in patients with chronic kidney disease (CKD). This has been attributed to abnormal HDL function in CKD.

View Article and Find Full Text PDF
Article Synopsis
  • Both NMR methods showed less than 5.5% difference from traditional ß-quantification measurements for total, LDL, and HDL cholesterol, and triglycerides, indicating strong correlation (r > 0.93) for most lipids, although HDL cholesterol showed weaker correlation.
  • The findings suggest that while both NMR methods are reliable for standard lipid measurement, improved harmonization is needed for better comparability of lipoprotein particle concentration data.
View Article and Find Full Text PDF

Background and Objective: Small, dense low-density lipoproteins (LDLs) are considered more atherogenic than normal size LDLs. However, the measurement of small, dense LDLs requires sophisticated laboratory methods, such as ultracentrifugation, gradient gel electrophoresis, or nuclear magnetic resonance. We aimed to analyze whether the LDL apolipoprotein B (LDLapoB)-to-LDL cholesterol (LDLC) ratio is associated with cardiovascular mortality and whether this ratio represents a biomarker for small, dense LDLs.

View Article and Find Full Text PDF