AimObesity and especially hypertrophy of epicardial adipose tissue accelerate coronary atherogenesis. We aimed at comparing levels of inflammatory and atherogenic hormones from adipose tissue in the pericardial fluid and circulation of cardiovascular disease patients.Methods and ResultsVenous plasma (P) and pericardial fluid (PF) were obtained from elective cardiothoracic surgery patients (n = 37). Concentrations of leptin, adipocyte fatty acid-binding protein (A-FABP) and adiponectin (APN) were determined by enzyme-linked immunosorbent assays (ELISA). The median concentration of leptin in PF (4.3 (interquartile range: 2.8–9.1) μg/L) was comparable to that in P (5.9 (2.2–11) μg/L) and these were significantly correlated to most of the same patient characteristics. The concentration of A-FABP was markedly higher (73 (28–124) versus 8.4 (5.2–14) μg/L) and that of APN was markedly lower (2.8 (1.7–4.2) versus 13 (7.2–19) mg/L) in PF compared to P. APN in PF was unlike in P not significantly related to age, body mass index, plasma triglycerides or coronary artery disease. PF levels of APN, but not A-FABP, were related to the size of paracardial adipocytes. PF levels of APN and A-FABP were not related to the immunoreactivity of paracardial adipocytes for these proteins.ConclusionIn cardiac and vascular disease patients, PF is enriched in A-FABP and poor in APN. This adipokine microenvironment is more likely determined by the heart than by the circulation or paracardial adipose tissue.
AimsLipocalin‐2 is a pro‐inflammatory molecule characterized by a highly diversified pattern of expression and structure–functional relationships. In vivo, this molecule exists as multiple variants due to post‐translational modifications and/or protein–protein interactions. Lipocalin‐2 is modified by polyamination, which enhances the clearance of this protein from the circulation and prevents its excessive accumulation in tissues. On the other hand, animal studies suggest that non‐polyaminated lipocalin‐2 (npLcn2) plays a causal role in the pathogenesis of obesity‐associated medical complications. The present study examined the presence of npLcn2 in samples from healthy volunteers or patients with cardiac abnormalities and evaluated npLcn2 as a biomarker for cardiometabolic risk assessment.Methods and resultsImmunoassays were developed to quantify npLcn2 in blood and urine samples collected from 100 volunteers (59 men and 41 women), or venous plasma and pericardial fluid samples obtained from 37 cardiothoracic surgery patients. In healthy volunteers, npLcn2 levels in serum are significantly higher in obese and overweight than in lean subjects. After adjustment for age, gender, smoking, and body mass index (BMI), serum npLcn2 levels are positively correlated with heart rate, circulating triglycerides, high‐sensitivity C‐reactive protein (hsCRP), and creatinine in plasma. The npLcn2 levels in urine are significantly increased in subjects with metabolic syndrome and positively correlated with BMI, heart rate, circulating triglycerides, and urinary aldosterone. In cardiothoracic surgery patients, the circulating concentrations of npLcn2 are higher (more than two‐fold) than those of healthy volunteers and positively correlated with the accumulation of this protein in the pericardial fluid. Heart failure patients exhibit excessive expression and distribution of npLcn2 in mesothelial cells and adipocytes of the parietal pericardium, which are significantly correlated with the elevated plasma levels of npLcn2, total cholesterol, and creatinine.ConclusionsQuantitative and qualitative evaluation of npLcn2 in human biofluid samples and tissue samples can be applied for risk assessment of healthy individuals and disease management of patients with obesity‐related cardiometabolic and renal complications.
BackgroundThe pericardial fluid may be representative of the interstitium of the heart. The aim of this study was to discriminate in cardiovascular disease patients between adipocytokines that are produced locally by the heart and those supplied by the circulation.MethodsEnzyme-linked immunosorbent assays (ELISA) were used to determine levels of N-terminal pro-brain natriuretic peptide (NT-pBNP), fatty acid-binding protein 4 (FABP4), leptin, lipocalin-2, neutrophil elastase, proteinase-3, high sensitivity C-reactive protein (hsCRP) and adiponectin in venous plasma and pericardial fluid harvested during elective cardio-thoracic surgery (n = 132–152).ResultsIn pericardial fluid compared to plasma, the levels were significantly smaller (p < 0.001) for leptin, lipocalin-2, neutrophil elastase, proteinase-3, hsCRP and adiponectin. For these biomarkers, the ratio of pericardial fluid-to-plasma level ([PF]/[P], median (interquartile range)) was 0.65 (0.47–1.01), 0.78 (0.56–1.09), 0.23 (0.11–0.60), 0.17 (0.09–0.36), 0.14 (0.08–0.35), and 0.25 (0.15–0.34), respectively. In contrast, pericardial fluid was significantly enriched (p < 0.001) in NT-pBNP ([PF]/[P]: 1.9 (1.06–2.73)) and even more so for FABP4 ([PF]/[P]: 3.90 (1.47–9.77)). Moreover, in pericardial fluid, the adipocytokines interrelated all significantly positive and correlated negative to hsCRP, whereas for NT-pBNP only a significantly positive correlation with adiponectin was found. These interrelations were distinct from those in the plasma, as were the correlations of the pericardial biomarkers with patient characteristics compared to plasma.ConclusionsIn cardiovascular disease patients, the pericardial cavity is a distinct adipocytokine microenvironment in which especially FABP4 is mainly derived from the heart.
One of the pathways involved in the pathogenesis of diabetic complications is the formation of excessive levels of advanced glycation end (AGE) products. Nɛ-carboxymethyllysine (CML) is one of the best-characterized AGEs. Because little is known about the effects of AGEs on pancreatic beta cells, we investigated the effect of CML on human pancreatic cells and determined the activity and gene expression of glutathione system components. CML at a concentration of 0.5 mM induced cell death in human pancreatic beta cells, which was accompanied by increased intracellular oxidative stress. No changes in the gene expression of the receptor for AGEs (RAGE) were found, although an increase in the level of a target cytokine of RAGE after CML exposure was observed. Additionally we found that CML lowered the levels of GSH and affected the activity and expression of other components of the glutathione system. These changes indicate that the cells are even more vulnerable for oxidative stress after exposure to CML. Since beta cells are low in antioxidant enzymes and repair for oxidized DNA, CML, but most likely also other AGEs, accelerates beta cell dysfunction and increases beta cell death during chronic hyperglycemia.
The striatum is known to play a primary role in procedural learning. In this study, the authors simultaneously assessed the effects of two antipsychotic drugs on procedural learning and on striatal dopamine (D2) receptor occupancy. Twenty-seven patients receiving either olanzapine or haloperidol as antipsychotic medication were assessed with the Computed Visual Tracking Task (CVTT) and Single Photon Emission Computed Tomography (SPECT) following the administration of Iodine 123-IBZM (123I-IBZM), a radioligand with a high affinity and specificity for the D2 receptors. The results showed poorer procedural learning in the haloperidol-treated patients than in normal control subjects, while no difference could be found between olanzapine-treated patients and normal control subjects. In the haloperidol but not the olanzapine group, significant correlations were found between procedural learning deficits and striatal D2 receptor occupancy. However, there was no significant difference in D2 receptor occupancy between olanzapine- and haloperidol-treated patients, and this may be related to the high doses of olanzapine and low doses of haloperidol administered. The authors concluded that: 1) striatal D2 receptor blockade may alter procedural learning in humans; and 2) olanzapine may have a protective effect on procedural learning, even at doses that produce striatal D2 receptor occupancy as high as that found with haloperidol. This protective effect of olanzapine may be related to its atypical pharmacological properties.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.