Interplay between the SAFE and the sphingolipid pathway for cardioprotection.

Aim: Activation of both the Survivor Activating Factor Enhancement (SAFE) pathway (including Tumor Necrosis Factor-alpha (TNF-α) and Signal Transducer and Activator of Transcription-3 (STAT-3)) and the sphingolipid signalling pathway (including sphingosine kinase-1 (SK1) and sphingosine-1 phosphate (S1P)) play a key role in promoting cardioprotection against ischemia-reperfusion injury (IRI). We investigated whether the activation of the SAFE pathway by exogenous S1P is dependent on the activation of SK1 for cardioprotection.

Materials And Methods: Isolated cardiomyocytes from TNF-α knockout (KO) mice, cardiomyocyte-specific STAT-3 KO mice and their wild-type (WT) littermates were exposed to simulated ischemia in the presence of a trigger of the SAFE pathway (S1P) and SK1 inhibitor (SK1-I).

People living with HIV display increased anti-apolipoprotein A1 auto-antibodies, inflammation, and kynurenine metabolites: a case-control study.

Objective: This study aimed to study the relationship between auto-antibodies against apolipoprotein A1 (anti-apoA1 IgG), human immunodeficiency virus (HIV) infection, anti-retroviral therapy (ART), and the tryptophan pathways in HIV-related cardiovascular disease.

Design: This case-control study conducted in South Africa consisted of control volunteers ( = 50), people living with HIV (PLWH) on ART ( = 50), and untreated PLWH ( = 44). Cardiovascular risk scores were determined, vascular measures were performed, and an extensive biochemical characterisation (routine, metabolomic, and inflammatory systemic profiles) was performed.

Ferritin: A Biomarker Requiring Caution in Clinical Decision.

Objectives: To determine the ferritin inter-assay differences between three "Conformité Européenne" (CE) marked tests, the impact on reference intervals (RI), and the proportion of individuals with iron deficiency (ID), we used plasma and serum from healthy blood donors (HBD) recruited in three different Switzerland regions.

Design And Methods: Heparinized plasma and serum from HBD were obtained from three different transfusion centers in Switzerland (Fribourg, Geneva, and Neuchatel). One hundred forty samples were recruited per center and per matrix, with a gender ratio of 50%, for a total of 420 HBD samples available per matrix.

Plasma biomarkers for Alzheimer's disease: a field-test in a memory clinic.

Background: The key Alzheimer's disease (AD) biomarkers are traditionally measured with techniques/exams that are either expensive (amyloid-positron emission tomography (PET) and tau-PET), invasive (cerebrospinal fluid Aβ and p-tau), or poorly specific (atrophy on MRI and hypometabolism on fluorodeoxyglucose-PET). Recently developed plasma biomarkers could significantly enhance the efficiency of the diagnostic pathway in memory clinics and improve patient care. This study aimed to: (1) confirm the correlations between plasma and traditional AD biomarkers, (2) assess the diagnostic accuracy of plasma biomarkers as compared with traditional biomarkers, and (3) estimate the proportion of traditional exams potentially saved thanks to the use of plasma biomarkers.

Giant Cell Tumor with Fracture of the Proximal Radius - Reconstructive Surgery with Radius Allograft.

Introduction: Giant cell tumor (GCT) of bone is a locally aggressive benign neoplasm that accounts for 4-10% of all primary bone tumors. It affects mostly young adults and occurs more frequently at the bones around the knee followed by the distal radius and the sacrum. Surgical treatment with curettage is the optimal treatment for local tumor control, but it can be associated to suboptimal functional outcome when located in periarticular regions.

Sphingosine-1-phosphate as a key player of insulin secretion induced by high-density lipoprotein treatment.

Beta cell failure is one of the most important features of type 2 diabetes mellitus (T2DM). High-density lipoprotein (HDL) has been proposed to improve β-cell function. However, the mechanisms involved in this process are still poorly understood.

Auto-antibodies against apolipoprotein A-1 block cancer cells proliferation and induce apoptosis.

Auto-antibodies against apoA-1 (anti-apoA-1 IgGs) have been identified as important actors of atherosclerosis development through pro-inflammatory and pro-atherogenic properties and to also induce apoptosis in tumoral neuronal and lymphocyte derived cell lines through unknown mechanisms. The purpose of this study was to explore the cellular pathways involved in tumoral cell survival modulated by anti-apoA-1 antibodies. We observed that anti-apoA-1 antibodies induce growth arrest (in G2/M phase) and cell apoptosis through caspase 3 activation, accompanied by a selective p53 phosphorylation on serine 15.

HIV-related cardiovascular disease: any role for high-density lipoproteins?

The introduction of antiretroviral therapy (ART) has improved the life expectancy of patients infected with human immunodeficiency virus (HIV). However, this population is at an increased risk for noncommunicable diseases, including atherosclerotic cardiovascular disease (CVD). Both ART and viral infection may be potential contributors to the pathophysiology of HIV-related CVD.

High-density lipoprotein cholesterol efflux capacity and cardiovascular risk in autoimmune and non-autoimmune diseases.

Functional assessment of cholesterol efflux capacity (CEC) to high-density lipoprotein (HDL) is an emerging tool for evaluating morbidity and mortality associated with cardiovascular disease (CVD). By promoting macrophage reverse cholesterol transport (RCT), HDL-mediated CEC is believed to play an important role in atherosclerotic lesion progression in the vessel wall. Furthermore, recent evidence indicates that the typical inverse associations between various forms of CEC and CV events may be strongly modulated by environmental systemic factors and traditional CV risk factors, in addition to autoimmune diseases.

Anti-ApoA-1 IgGs in Familial Hypercholesterolemia Display Paradoxical Associations with Lipid Profile and Promote Foam Cell Formation.

Aims: Anti-Apolipoprotein A-1 autoantibodies (anti-ApoA-1 IgG) promote atherogenesis via innate immune receptors, and may impair cellular cholesterol homeostasis (CH). We explored the presence of anti-ApoA-1 IgG in children (5-15 years old) with or without familial hypercholesterolemia (FH), analyzing their association with lipid profiles, and studied their in vitro effects on foam cell formation, gene regulation, and their functional impact on cholesterol passive diffusion (PD).

Methods: Anti-ApoA-1 IgG and lipid profiles were measured on 29 FH and 25 healthy children.

Humoral Immunity Against HDL Particle: A New Perspective in Cardiovascular Diseases?

Background: Autoimmune diseases are closely associated with cardiovascular diseases (CVD). Over the last decades, the comprehension of atherosclerosis, the principal initiator of CVD, evolved from a lipidcentered disease to a predominant inflammatory and immune response-driven disease displaying features of autoimmunity against a broad range of auto-antigens, including lipoproteins. Among them, high density lipoproteins (HDL) are important actors of cholesterol transport and bear several anti-atherogenic properties, raising a growing interest as therapeutic targets to decrease atherosclerosis and CVD burden, with nevertheless rather disappointing results so far.

HDL protects against myocardial ischemia reperfusion injury via miR-34b and miR-337 expression which requires STAT3.

Purpose: High density lipoprotein (HDL) protects against myocardial infarction via mechanisms that remain unclear. STAT3 (signal transducer and activator of transcription 3) plays a key role in HDL-induced cardioprotection. In the heart, microRNAs (miRNAs) are involved in ischemia reperfusion injury.

ELISA methods comparison for the detection of auto-antibodies against apolipoprotein A1.

Background: Autoantibodies against apolipoprotein A1 (anti-apoA1 IgG) have emerged as an independent biomarker for cardiovascular disease and mortality. Across studies, different ELISA methods have been used to measure the level of circulating anti-apoA1 IgG which could lead to substantial result differences between assays.

Objectives: To make a comparative study of available anti-apoA1 IgG detection methods and to determine whether the choice of matrix sample (serum vs plasma) could influence the results.

Pharmacological Intervention to Modulate HDL: What Do We Target?

The cholesterol concentrations of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) have traditionally served as risk factors for cardiovascular disease. As such, novel therapeutic interventions aiming to raise HDL cholesterol have been tested in the clinical setting. However, most trials led to a significant increase in HDL cholesterol with no improvement in cardiovascular events.

Impact of long distance rowing on biological health: A pilot study.

Objectives: To determine the impact of long distance rowing (160km, nonstop) on standard biological parameters and to study the relation between inflammation, myocardial necrosis, lipid profile, heart rate and energy expenditure.

Methods: Electrolytes, lipid profile, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), procalcitonin (PCT), high-sensitive troponin T (hs-cTnT), and N-terminal pro-brain natriuretic peptide (NT-proBNP), were measured on non-fasting venous blood samples collected 8h before and after the rowing race on five healthy competitors. Heart rate and energy expenditure were measured using sporting self-measurement devices.

High-density lipoprotein from end-stage renal disease patients exhibits superior cardioprotection and increase in sphingosine-1-phosphate.

Background: Chronic kidney disease (CKD) exacerbates the risk of death due to cardiovascular disease (CVD). Modifications to blood lipid metabolism which manifest as increases in circulating triglycerides and reductions in high-density lipoprotein (HDL) cholesterol are thought to contribute to increased risk. In CKD patients, higher HDL cholesterol levels were not associated with reduced mortality risk.

High-density lipoprotein-associated sphingosine-1-phosphate activity in heterozygous familial hypercholesterolaemia.

Background: Patients with heterozygous familial hypercholesterolaemia (FH) suffer from high plasma cholesterol and an environment of increased oxidative stress. We examined its potential effects on high-density lipoprotein (HDL)-associated sphingosine-1-phosphate (S1P) content (HDL-S1P) and HDL-mediated protection against oxidative stress, both with and without statin treatment.

Materials And Methods: In a case-control study, HDL was isolated from 12 FH patients with and without statin treatment and from 12 healthy controls.

Abca1 deficiency protects the heart against myocardial infarction-induced injury.

Background And Aims: We explored the role of ATP-binding cassette transporter A1 (Abca1), in post-myocardial infarction (MI) cardiac injury.

Methods: In Abca1(-/-) mice, wild type (WT) mice, and WT mice transplanted with Abca1(-/-) or WT bone marrow, an MI was induced in vivo. Furthermore, an ex vivo MI was induced in isolated Abca1(-/-) and WT hearts.

Association between ethnicity and obesity with high-density lipoprotein (HDL) function and subclass distribution.

Background: Obesity and low high-density lipoprotein-cholesterol (HDL-C) levels are associated with cardiovascular risk. Surprisingly, despite a greater prevalence of obesity and lower HDL concentrations than white women, black South African women are relatively protected against ischaemic heart disease.

Methods: We investigated whether this apparent discrepancy may be related to different HDL function and subclass distribution in black and white, normal-weight and obese South African women (n = 40).

Diabetes Mellitus Is Associated With Reduced High-Density Lipoprotein Sphingosine-1-Phosphate Content and Impaired High-Density Lipoprotein Cardiac Cell Protection.

Objective: The dyslipidemia of type 2 diabetes mellitus has multiple etiologies and impairs lipoprotein functionality, thereby increasing risk for cardiovascular disease. High-density lipoproteins (HDLs) have several beneficial effects, notably protecting the heart from myocardial ischemia. We hypothesized that glycation of HDL could compromise this cardioprotective effect.

Sphingosine-1-phosphate reduces ischaemia-reperfusion injury by phosphorylating the gap junction protein Connexin43.

Aim: Increasing evidence points to lipoprotein composition rather than reverse cholesterol transport in the cardioprotective properties of high-density lipoproteins (HDLs). HDL binding to receptors at the surface of cardiomyocytes activates signalling pathways promoting survival, but downstream targets are largely unknown. Here, we investigate the pathways by which the sphingosine-1-phosphate (S1P) constituent of HDL limits cell death induced by cardiac ischaemia-reperfusion (I/R).

CD14 as a Mediator of the Mineralocorticoid Receptor-Dependent Anti-apolipoprotein A-1 IgG Chronotropic Effect on Cardiomyocytes.

In vitro and animal studies point to autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) as possible mediators of cardiovascular (CV) disease involving several mechanisms such as basal heart rate interference mediated by a mineralocorticoid receptor-dependent L-type calcium channel activation, and a direct pro-inflammatory effect through the engagement of the toll-like receptor (TLR) 2/CD14 complex. Nevertheless, the possible implication of these receptors in the pro-arrhythmogenic effect of anti-apoA-1 antibodies remains elusive. We aimed at determining whether CD14 and TLRs could mediate the anti-apoA-1 IgG chronotropic response in neonatal rat ventricular cardiomyocytes (NRVC).

Improving reconstituted HDL composition for efficient post-ischemic reduction of ischemia reperfusion injury.

Background: New evidence shows that high density lipoproteins (HDL) have protective effects beyond their role in reverse cholesterol transport. Reconstituted HDL (rHDL) offer an attractive means of clinically exploiting these novel effects including cardioprotection against ischemia reperfusion injury (IRI). However, basic rHDL composition is limited to apolipoprotein AI (apoAI) and phospholipids; addition of bioactive compound may enhance its beneficial effects.

Therapeutic potential of HDL in cardioprotection and tissue repair.

Epidemiological studies support a strong association between high-density lipoprotein (HDL) cholesterol levels and heart failure incidence. Experimental evidence from different angles supports the view that low HDL is unlikely an innocent bystander in the development of heart failure. HDL exerts direct cardioprotective effects, which are mediated via its interactions with the myocardium and more specifically with cardiomyocytes.

High density lipoproteins and ischemia reperfusion injury: the therapeutic potential of HDL to modulate cell survival pathways.

The clinical importance of high density lipoproteins has grown in recent years with demonstrations of their impact on diverse pathological mechanisms implicated not only in vascular disease, but also in other physiological systems. This is related to the multiple functions associated with high-density lipoproteins (HDL), notably their ability to limit oxidant and inflammatory processes, which are common to different disease states. A second feature of particular clinical relevance is the possibility of synthesising a simplified form of HDL that exhibits some of the functions of the mature lipoprotein.