Sex-Related Differences in the Associations between Adiponectin and Serum Lipoproteins in Healthy Subjects and Patients with Metabolic Syndrome.

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.

Serum Levels of Adiponectin Are Strongly Associated with Lipoprotein Subclasses in Healthy Volunteers but Not in Patients with Metabolic Syndrome.

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).

The 10 essential questions regarding lipoprotein(a).

Purpose Of Review: Lp(a) is one of the most atherogenic lipoproteins, and significant progress has been made to understand its pathophysiology over the last 20 years. There are now selective therapies in late-stage clinical trials to lower Lp(a). Yet there are many outstanding questions about Lp(a).

Development of an LC-MRM-MS-Based Candidate Reference Measurement Procedure for Standardization of Serum Apolipoprotein (a) Tests.

Background: Medical results generated by European CE Marking for In Vitro Diagnostic or in-house tests should be traceable to higher order reference measurement systems (RMS), such as International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)-endorsed reference measurement procedures (RMPs) and reference materials. Currently, serum apolipoprotein (a) [apo(a)] is recognized as a novel risk factor for cardiovascular risk assessment and patient management. The former RMS for serum apo(a) is no longer available; consequently, an International System of Units (SI)-traceable, ideally multiplexed, and sustainable RMS for apo(a) is needed.

Lp(a) and the Risk for Cardiovascular Disease: Focus on the Lp(a) Paradox in Diabetes Mellitus.

Lipoprotein(a) (Lp(a)) is one of the strongest causal risk factors of atherosclerotic disease. It is rich in cholesteryl ester and composed of apolipoprotein B and apo(a). Plasma Lp(a) levels are determined by apo(a) transcriptional activity driven by a direct repeat (DR) response element in the apo(a) promoter under the control of (HNF)4α Farnesoid-X receptor (FXR) ligands play a key role in the downregulation of expression.

Towards an SI-Traceable Reference Measurement System for Seven Serum Apolipoproteins Using Bottom-Up Quantitative Proteomics: Conceptual Approach Enabled by Cross-Disciplinary/Cross-Sector Collaboration.

Current dyslipidemia management in patients with atherosclerotic cardiovascular disease (ASCVD) is based on traditional serum lipids. Yet, there is some indication from basic research that serum apolipoproteins A-I, (a), B, C-I, C-II, C-III, and E may give better pathophysiological insight into the root causes of dyslipidemia. To facilitate the future adoption of clinical serum apolipoprotein (apo) profiling for precision medicine, strategies for accurate testing should be developed in advance.

Apolipoprotein C3 induces inflammation and organ damage by alternative inflammasome activation.

NLRP3-inflammasome-driven inflammation is involved in the pathogenesis of a variety of diseases. Identification of endogenous inflammasome activators is essential for the development of new anti-inflammatory treatment strategies. Here, we identified that apolipoprotein C3 (ApoC3) activates the NLRP3 inflammasome in human monocytes by inducing an alternative NLRP3 inflammasome via caspase-8 and dimerization of Toll-like receptors 2 and 4.

Comparison of lipoprotein (a) serum concentrations measured by six commercially available immunoassays.

Background And Aims: Lipoprotein (a) [Lp(a)] is an established causal risk factor for cardiovascular disease (CVD), independently of low-density lipoproteins (LDL) and other risk factors. The recognition of Lp(a) as an atherogenic molecule has raised the demand for reliable quantification methods in the clinical laboratory. The aim of this work is to compare commercial immunochemical assays.

Is Lp(a) ready for prime time use in the clinic? A pros-and-cons debate.

Lipoprotein (a) (Lp(a)) is a cholesterol-rich lipoprotein known since 1963. In spite of extensive research on Lp(a), there are still numerous gaps in our knowledge relating to its function, biosynthesis and catabolism. One reason for this might be that apo(a), the characteristic glycoprotein of Lp(a), is expressed only in primates.

Implications of cerebrovascular ATP-binding cassette transporter G1 (ABCG1) and apolipoprotein M in cholesterol transport at the blood-brain barrier.

Impaired cholesterol/lipoprotein metabolism is linked to neurodegenerative diseases such as Alzheimer's disease (AD). Cerebral cholesterol homeostasis is maintained by the highly efficient blood-brain barrier (BBB) and flux of the oxysterols 24(S)-hydroxycholesterol and 27-hydroxycholesterol, potent liver-X-receptor (LXR) activators. HDL and their apolipoproteins are crucial for cerebral lipid transfer, and loss of ATP binding cassette transporters (ABC)G1 and G4 results in toxic accumulation of oxysterols in the brain.

Homozygous familial hypercholesterolemia: Summarized case reports.

Background And Aims: Homozygous familial hypercholesterolemia (hoFH) is a rare genetic disorder with potential severe atherosclerosis in the pediatric age.

Methods: We report on 9 patients with hoFH, who had been diagnosed within the last 30 years and who were consequently treated with apheresis and drugs.

Results: Two deaths occurred: one at age 36 years and the other at age four and a half years before effective treatment was commenced.

Lipoprotein (a): a historical appraisal.

Initially, lipoprotein (a) [Lp(a)] was believed to be a genetic variant of lipoprotein (Lp)-B. Because its lipid moiety is almost identical to LDL, Lp(a) has been deliberately considered to be highly atherogenic. Lp(a) was detected in 1963 by Kare Berg, and individuals who were positive for this factor were called Lpa Lpa individuals were found more frequently in patients with coronary heart disease than in controls.

MiR-206 is expressed in pancreatic islets and regulates glucokinase activity.

Glucose homeostasis is a complex indispensable process, and its dysregulation causes hyperglycemia and type 2 diabetes mellitus. Glucokinase (GK) takes a central role in these pathways and is thus rate limiting for glucose-stimulated insulin secretion (GSIS) from pancreatic islets. Several reports have described the transcriptional regulation of Gck mRNA, whereas its posttranscriptional mechanisms of regulation, especially those involving microRNAs (miR), are poorly understood.

[New AHA and ACC guidelines on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk : Statement of the D•A•CH Society for Prevention of Cardiovascular Diseases, the Austrian Atherosclerosis Society and the Working Group on Lipids and Atherosclerosis (AGLA) of the Swiss Society for Cardiology].

Guidelines for the reduction of cholesterol to prevent atherosclerotic vascular events were recently released by the American Heart Association and the American College of Cardiology. The authors claim to refer entirely to evidence from randomized controlled trials, thereby confining their guidelines to statins as the primary therapeutic option. The guidelines derived from these trials do not specify treatment goals, but refer to the percentage of cholesterol reduction by statin medication with low, moderate, and high intensity.

New AHA and ACC guidelines on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk.

After the publication of the new guidelines of the European Society of Cardiology and the European Atherosclerosis Society for the prevention and treatment of dyslipidemias (Eur Heart J 32:1769-1818, 2011; Eur Heart J 33:1635-1701, 2012), a group of authors has recently published on behalf of the American Heart Association and the American College of Cardiology guidelines on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk (Circulation 2013). These new guidelines are supposed to replace the until now widely accepted, at least in the USA, recommendations of the National Cholesterol Education Program Adult Treatment Panel III from the years 2002 (Circulation 106:3143-3421, 2002) and 2004 (Circulation 110:227-39, 2004). Furthermore, they claim to be based mainly on hard evidence derived from the interpretation of results of prospective randomized controlled trials.

miR-206 controls LXRα expression and promotes LXR-mediated cholesterol efflux in macrophages.

Liver X receptors (LXRα and LXRβ) are key transcription factors in cholesterol metabolism that regulate cholesterol biosynthesis/efflux and bile acid metabolism/excretion in the liver and numerous organs. In macrophages, LXR signaling modulates cholesterol handling and the inflammatory response, pathways involved in atherosclerosis. Since regulatory pathways of LXR transcription control are well understood, in the present study we aimed at identifying post-transcriptional regulators of LXR activity.

When should we measure lipoprotein (a)?

Recently published epidemiological and genetic studies strongly suggest a causal relationship of elevated concentrations of lipoprotein (a) [Lp(a)] with cardiovascular disease (CVD), independent of low-density lipoproteins (LDLs), reduced high density lipoproteins (HDL), and other traditional CVD risk factors. The atherogenicity of Lp(a) at a molecular and cellular level is caused by interference with the fibrinolytic system, the affinity to secretory phospholipase A2, the interaction with extracellular matrix glycoproteins, and the binding to scavenger receptors on macrophages. Lipoprotein (a) plasma concentrations correlate significantly with the synthetic rate of apo(a) and recent studies demonstrate that apo(a) expression is inhibited by ligands for farnesoid X receptor.

Lipoprotein lipase in chronic lymphocytic leukaemia - strong biomarker with lack of functional significance.

In chronic lymphocytic leukaemia (CLL), lipoprotein lipase (LPL) mRNA overexpression is an established poor prognostic marker, its function, however, is poorly understood. Measuring extracellular LPL enzymatic activity and protein, we found no difference between levels in CLL patients and those of controls, both before and after heparin treatment in vivo and in vitro. Investigating LPL knock down effects, we determined five potential downstream targets, of which one gene, STXBP3, reportedly is involved in fatty acid metabolism.

Nicotinic acid inhibits hepatic APOA gene expression: studies in humans and in transgenic mice.

Elevated plasma lipoprotein(a) (LPA) levels are recognized as an independent risk factor for cardiovascular diseases. Our knowledge on LPA metabolism is incomplete, which makes it difficult to develop LPA-lowering medications. Nicotinic acid (NA) is the main drug recommended for the treatment of patients with increased plasma LPA concentrations.

FGF19 signaling cascade suppresses APOA gene expression.

Objective: Lipoprotein(a) is a highly atherogenic lipoprotein, whose metabolism is poorly understood. Currently no safe drugs exists that lower elevated plasma lipoprotein(a) concentrations. We therefore focused on molecular mechanisms that influence apolipoprotein(a) (APOA) biosynthesis.

Expression of fat mobilizing genes in human epicardial adipose tissue.

Background: Epicardial adipose tissue (EAT) mass correlates with metabolic syndrome and coronary artery disease (CAD). However, little is known about the expression of genes involved in triglyceride (TG) storage and mobilization in EAT. We therefore analyzed the expression of genes involved in fat mobilization in EAT in comparison to subcutaneous abdominal adipose tissue (AAT) in CAD patients and in controls.

Farnesoid X receptor represses hepatic human APOA gene expression.

High plasma concentrations of lipoprotein(a) [Lp(a), which is encoded by the APOA gene] increase an individual's risk of developing diseases, such as coronary artery diseases, restenosis, and stroke. Unfortunately, increased Lp(a) levels are minimally influenced by dietary changes or drug treatment. Further, the development of Lp(a)-specific medications has been hampered by limited knowledge of Lp(a) metabolism.

Synthetic LXR agonist suppresses endogenous cholesterol biosynthesis and efficiently lowers plasma cholesterol.

The liver X receptors (LXRs) are key regulators of genes involved in cholesterol homeostasis. Natural ligands and activators of LXRs are oxysterols. Numerous steroidal and non-steroidal synthetic LXR ligands are under development as potential drugs for individuals suffering from lipid disorders.