Kidney derived apolipoprotein M and its role in acute kidney injury.

Apolipoprotein M (apoM) is mainly expressed in liver and in proximal tubular epithelial cells in the kidney. In plasma, apoM associates with HDL particles via a retained signal peptide and carries sphingosine-1-phosphate (S1P), a small bioactive lipid. ApoM is undetectable in urine from healthy individuals but lack of megalin receptors in proximal tubuli cells induces loss of apoM into the urine.

Apolipoprotein M in patients with chronic kidney disease.

Background And Aims: Plasma apolipoprotein M (APOM) is bound to HDL-particles and has anti-atherogenic effects. The present study explored whether plasma APOM is reduced in patients with chronic kidney disease (CKD), and associated with cardiovascular disease (CVD). In addition, we tested the hypothesis that the excretion of APOM into the urine is increased in patients with kidney disease.

Diet-Induced Abdominal Obesity, Metabolic Changes, and Atherosclerosis in Hypercholesterolemic Minipigs.

Background: Obesity and metabolic syndrome (MetS) are major risk factors for atherosclerotic diseases; however, a causal link remains elusive. Animal models resembling human MetS and its complications, while important, are scarce. We aimed at developing a porcine model of human MetS.

Exercise and weight loss effects on cardiovascular risk factors in overweight men.

Both exercise training and weight loss reduce cardiovascular risk, but the independent importance of the two strategies is unclear. We aimed to investigate independent and combined effects of exercise training and weight loss on lipoproteins and dyslipidemia in overweight sedentary men. Sixty individuals were randomized to 12 wk of endurance training (T), energy-reduced diet (D), training and energy increased diet (T-iD), or control (C).

Effects of apolipoprotein M in uremic atherosclerosis.

Background And Aims: Chronic kidney disease is characterized by uremia and causes premature death, partly due to accelerated atherosclerosis. Apolipoprotein (apo) M is a plasma carrier protein for the lipid sphingosine-1-phosphate (S1P). The Apom-S1P complex associates with HDL, and may contribute to its anti-atherosclerotic effects.

HDL activation of endothelial sphingosine-1-phosphate receptor-1 (S1P) promotes regeneration and suppresses fibrosis in the liver.

Regeneration of hepatic sinusoidal vasculature is essential for non-fibrotic liver regrowth and restoration of its metabolic capacity. However, little is known about how this specialized vascular niche is regenerated. Here we show that activation of endothelial sphingosine-1-phosphate receptor-1 (S1P) by its natural ligand bound to HDL (HDL-S1P) induces liver regeneration and curtails fibrosis.

Effect of 12-O-tetradecanoylphorbol-13-acetate-induced psoriasis-like skin lesions on systemic inflammation and atherosclerosis in hypercholesterolaemic apolipoprotein E deficient mice.

Background: Risk of cardiovascular disease is increased in patients with psoriasis, but molecular mechanisms linking the two conditions have not been clearly established. Lack of appropriate animal models has hampered generation of new knowledge in this area of research and we therefore sought to develop an animal model with combined atherosclerosis and psoriasis-like skin inflammation.

Methods: Topical 12-O-tetradecanoylphorbol-13-acetate (TPA) was applied to the ears twice per week for 8 weeks in atherosclerosis-prone apolipoprotein E deficient (ApoE(-/-)) mice.

Treatment with a human recombinant monoclonal IgG antibody against oxidized LDL in atherosclerosis-prone pigs reduces cathepsin S in coronary lesions.

Background: Immunization with oxidized LDL (oxLDL) reduces atherosclerosis in rodents. We tested the hypothesis that treatment with a human recombinant monoclonal antibody against oxLDL will reduce the burden or composition of atherosclerotic lesions in hypercholesterolemic minipigs.

Methods And Results: Thirty-eight hypercholesterolemic minipigs with defective LDL receptors were injected with an oxLDL antibody or placebo weekly for 12weeks.

Urinary apolipoprotein M as a biomarker of acute kidney injury in children undergoing heart surgery.

Aim: To investigate whether apoM is excreted in urine of children undergoing heart surgery and the potential of apoM as early biomarker of acute kidney injury (AKI).

Materials & Methods: Urine was collected in children undergoing heart surgery. ApoM was measured with ELISA.

Diet-induced pre-diabetes slows cardiac conductance and promotes arrhythmogenesis.

Background: Type 2 diabetes is associated with abnormal electrical conduction and sudden cardiac death, but the pathogenic mechanism remains unknown. This study describes electrophysiological alterations in a diet-induced pre-diabetic rat model and examines the underlying mechanism.

Methods: Sprague-Dawley rats were fed either high-fat diet and fructose water or normal chow and water for 6 weeks.

Genetic analysis of ligation-induced neointima formation in an F2 intercross of C57BL/6 and FVB/N inbred mouse strains.

Objective: Proliferation and migration of vascular smooth muscle cells (SMCs) are central for arterial diseases including atherosclerosis and restenosis. We hypothesized that the underlying mechanisms may be modeled by carotid ligation in mice. In FVB/N inbred mice, ligation leads to abundant neointima formation with proliferating media-derived SMCs, whereas in C57BL/6 mice hardly any neointima is formed.

Protein unfolding allows use of commercial antibodies in an apolipoprotein M sandwich ELISA.

apoM is a member of the lipocalin superfamily and circulates in plasma attached to HDL particles. apoM plays a role in cholesterol metabolism and has recently been identified as transporter for the signaling lipid, sphingosine-1-phosphate (S1P), in plasma. S1P is implicated in several inflammatory diseases such as multiple sclerosis and rheumatoid arthritis.

Polybrominated diphenyl ethers and perfluoroalkyl substances in serum of pregnant women: levels, correlations, and potential health implications.

Polybrominated diphenyl ethers (PBDEs), a group of flame retardants, and perfluoroalkyl substances (PFASs) were analysed in serum samples of pregnant women from Denmark to provide information about their exposure and to study indications of common exposure pathways. The main BDE congener was the fully brominated BDE-209 with a median value of 7.5 ng/g lipid (46 pg/mL; 9.

Apolipoprotein M promotes mobilization of cellular cholesterol in vivo.

Objective: The HDL associated apolipoprotein M (apoM) protects against experimental atherosclerosis but the mechanism is unknown. ApoM increases prebeta-HDL formation. We explored whether plasma apoM affects mobilization of cholesterol from peripheral cells in mice.

Apolipoprotein M: bridging HDL and endothelial function.

Purpose Of Review: The review will address the potential roles of apolipoprotein M (apoM) as a carrier protein and modulator of sphingosine-1-phosphate (S1P) bioactivity.

Recent Findings: Recombinant apoM can bind small lipids such as retinoic acid, oxidized phospholipids, and S1P. Thus, the effects of apoM may be pleiotrophic.

Osteopontin deficiency dampens the pro-atherogenic effect of uraemia.

Aims: Uraemia is a strong risk factor for cardiovascular disease. Osteopontin (OPN) is highly expressed in aortas of uraemic apolipoprotein E knockout (E KO) mice. OPN affects key atherogenic processes, i.

NT-ProBNP independently predicts long-term mortality in patients admitted for coronary angiography.

Recently, research interests are focussed on biomarkers to predict the outcome in patients with coronary artery disease (CAD). We examined whether the levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) could predict outcome in patients who underwent elective or acute coronary angiography (CAG). A total of 337 patients with suspected CAD who underwent elective or acute CAG were followed up for a mean period of 6.

Hypoxia changes the expression of the epidermal growth factor (EGF) system in human hearts and cultured cardiomyocytes.

Background: The epidermal growth factor (EGF) receptors HER2 and HER4 and the ligands HB-EGF and NRG1 are crucial for heart development. The purpose of our study was to investigate the role of the complete EGF system in relation to hypoxia of the heart.

Methodology/principal Findings: We examined the mRNA expression by real time PCR of the 4 receptors and 12 ligands from the EGF-system in paired normoxic and hypoxic biopsies isolated from human hearts during coronary artery bypass operation.

Apolipoprotein M--a new biomarker in sepsis.

Sepsis is one of the leading causes of mortality in non-cardiac intensive care units, and the need for markers of progression and severity are high. Also, treatment of sepsis is highly debated and potential new targets of treatment are of great interest. In the previous issue of Critical Care Kumaraswamy and colleagues have investigated whether plasma apolipoprotein M (apoM) is affected during different grades of sepsis, septic shock and systemic inflammatory response syndrome.