Volume Status in Patients on Peritoneal Dialysis: The Role of Apelin and Bio-Impedance Spectroscopy

One of the main factors determining the survival of peritoneal dialysis (PD) patients is volume status. We aimed to investigate hydration status of PD patients by bio-impedance spectroscopy (BIS) and echocardiography and to study the relation of them with apelin, which has effects related with volume status like vasodilation, positive inotropism, and inhibition of ADH release and RAS antagonism. Chronic PD patients without active cardiac disease or clinically prominent hypervolemia were included. Besides the demographic, clinical, and laboratory data, BIS and echocardiographic findings together with apelin levels were recorded. The study included 21 patients. Of them, eight patients were euvolemic, one patient was hypovolemic, and others have some degree of overhydration (1.1–6.8 L) with BIS, although all were euvolemic clinically. Mean apelin level was 1.49 ± 0.49 ng/mL. Apelin level was positively correlated with ejection fraction and negatively with total body water (TBW), intracellular and extracellular water, lean tissue mass, and left atrium diameter. On linear regression model, TBW was the major determinant of apelin. Although apelin is expected to increase in hypervolemic patients, the negative correlation with body water in this study may be related with yet unknown role of apelin in dialyzed patients. They may have important roles in volume status in future.     

Clinical significance of apelin in the treatment of type 2 diabetic peripheral neuropathy

Background:Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes. As apelin is an adipocytokine closely associated with diabetes, this study explored the clinical significance of serum apelin levels in patients with type 2 DPN before and after treatment.Methods:In total, 44 patients with T2DM without DPN (non-DPN group), 41 patients with DPN who received antihyperglycemic treatment (DPN-A group), 44 patients with DPN who received antihyperglycemic treatment combined with nutritional neurotherapy (DPN-B group), and 40 healthy control individuals (NC group) were selected continuously enrolled in the present study. Enzyme-linked immunosorbent assays (ELISA) were performed to determine serum levels of apelin and tumor necrosis factor-α (TNF-α). Related apelin, fasting blood glucose (FBG), glycosylated hemoglobin A1c, TNF-α, body mass index, fasting C peptide, and nerve conduction velocity (NCV) were recorded in each group before and after treatment.Results:Serum levels of apelin and TNF-α were higher in patients with diabetes than those in the NC group, as well as in the DPN group as compared to the non-DPN group; furthermore, some NCV values were significantly reduced in the DPN group. After treatment, the serum levels of apelin, TNF-α, and FBG reduced in patients with diabetes; moreover, apelin levels were found significantly lower in the DPN-B group as compared to the DPN-A group, while some NCV values significantly increased in the DPN-B group. Apelin was negatively correlated with part of NCV values and positively correlated with TNF-α and FBG (P < .01).Conclusion:Our results show that the increase in serum apelin levels is an important clinical reference index for DPN, while a decrease indicates that the DPN treatment is effective.     

Therapeutic Benefit and Gene Network Regulation by Combined Gene Transfer of Apelin,FGF2, and SERCA2a into Ischemic Heart

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不同类型房颤患者血浆apelin的水平及其意义

目的：观察不同类型房颤患者血浆apelin的水平及其与N端B型利钠肽前体（NT-proBNP）、左房内径（LAD）的关系。方法85例房颤患者分为阵发性房颤组（B组）31例、持续性房颤组（C组）29例和永久性房颤组（D组）25例,同期非房颤住院患者为对照组（A组）26例。检测血浆apelin、NT-proBNP,并行心脏超声测定LAD,进行统计学分析。结果与A组相比,B组、C组、D组血浆apelin水平均明显降低（P均＜0．05）,而D组明显低于B组和C组（P均＜0．05）,B组与C组之间比较,差异无统计学意义（P＞0．05）;与A组相比,B组、C组、D组NT-proBNP显著升高（P均＜0．05）,D组最高,而B组与C组之间比较,差异无统计学意义（P＞0．05）;LAD在A组、B组、C组、D组之间有明显差异,呈依次递增（P＜0．05）。多元相关分析显示：血浆 apelin 与NT-proBNP、LAD负相关,（r＝-0．28、-0．32,P均＜0．05）。结论不同类型房颤患者血浆apelin水平降低,可能通过抗纤维化参与心房重构,与房颤的发生和维持相关。     

The effects of water immersion and restraint stress on the expressions of apelin,apelin receptor (APJR) and apoptosis rate in the rat heart

Apelin has been identified as an endogenous ligand of the orphan G-protein-coupled apelin receptor (APJR). These receptors are widely expressed in the central nervous system and periphery and play a role in the regulation of fluid and glucose homeostasis, feeding behavior, vessel formation, cell proliferation and immunity. We aimed to investigate whether water immersion and restraint stress have effects on apelin and APJR expression and apoptosis in heart tissue of male Wistar rats. The cardiac tissues were obtained from control, water immersion and restraint stress (WIRS) and apelin antagonist (F13A) + WIRS groups of rats and embedded in paraffin wax. Immunohistochemical staining methods were used to localize apelin, APJR and TUNEL immunopositive cells. H-SCORE was used for semi-quantitative determinations. Apelin protein levels were determined by Western blot in the cardiac tissues and plasma corticosteroid levels were measured by enzyme immunoassay (EIA). Apelin immunolocalization was found especially in endothelial cells and mast cells and faintly in cardiomyocytes, APJR immunostaining was shown in endothelial cells and cardiomyocytes, and TUNEL reaction was observed in endothelial cells and in some fibroblasts. Apelin expression was significantly increased in the WIRS and F13A + WIRS groups compared to the control group. The APJR reaction was similar in all groups. The number of TUNEL-positive cells was significantly higher in the F13A + WIRS group than that of the control group. Our study showed that WIRS for 6 h increased plasma corticosterone levels and cardiac apelin expression in rats. The increased levels of apelin inhibited stress-induced apoptosis in heart. These results may be important for the therapeutic approach to a variety of stress-related heart disease.     

Opioid receptors mediate inotropic and depressor effects of apelin in rats with 2K1C‐induced chronic renovascular hypertension

Apelin receptors (APJ) cross‐talk with other G‐protein‐coupled receptors. However, the role of APJ interaction with opioid receptors (OPR) on the cardiovascular effects of apelin in hypertension is not clear. Renovascular hypertension was induced by placing a Plexiglas clip on the left kidney of rats. After 16 weeks, F13A (an APJ antagonist), naloxone (a general OPR inhibitor), and nor‐binaltorphimine dihydrochloride (nor‐BNI; a selective inhibitor of KOR) were given prior to injections of apelin at doses of 40 and 60 μg/kg. The arterial systolic/diastolic blood pressure and left ventricular contractility responses were then evaluated. The arterial systolic/diastolic blood pressure in sham and 2K1C rats was 110/71 mm Hg and 171/124 mm Hg, respectively. The hypotensive effects of apelin at both doses were inhibited by F13A and naloxone. Nor‐BNI completely inhibited the effects of apelin 40 on arterial pressure, and decreased the effects of 60 μg/kg. KOR inhibition also prevented the compensation for the decrease in the left ventricle +dp/dt max and ?dp/dt max caused by apelin 60. The simultaneous inhibition of OPR and APJ reduced arterial pressure and increased cardiac contractility. Findings showed that the OPR, particularly KOR, mediate the inotropic, lusitropic, and depressor effects of apelin. The interaction of the OPR and APJ augments the inotropic and vasodepressor effects of apelin. This interaction may have potential clinical applications in cardiac failure since opioids are currently used in the treatment of myocardial infarction and stroke, and apelin has been introduced as a potential therapeutic agent in cardiovascular complications.     

High Hydrostatic Pressure Processing of Human Milk Increases Apelin and GLP-1 Contents to Modulate Gut Contraction and Glucose Metabolism in Mice Compared to Holder Pasteurization

Background: High hydrostatic pressure (HHP) processing is a non-thermal method proposed as an alternative to Holder pasteurization (HoP) for the sterilization of human breast milk (BM). HHP preserves numerous milk bioactive factors that are degraded by HoP, but no data are available for milk apelin and glucagon-like peptide 1 (GLP-1), two hormones implicated in the control of glucose metabolism directly and via the gut–brain axis. This study aims to determine the effects of HoP and HHP processing on apelin and GLP-1 concentrations in BM and to test the effect of oral treatments with HoP- and HHP-BM on intestinal contractions and glucose metabolism in adult mice. Methods: Mice were treated by daily oral gavages with HoP- or HHP-BM during one week before intestinal contractions, and glucose tolerance was assessed. mRNA expression of enteric neuronal enzymes known to control intestinal contraction was measured. Results: HoP-BM displayed a reduced concentration of apelin and GLP-1, whereas HHP processing preserved these hormones close to their initial levels in raw milk. Chronic HHP-BM administration to mice increased ileal mRNA nNos expression level leading to a decrease in gut contraction associated with improved glucose tolerance. Conclusion: In comparison to HoP, HPP processing of BM preserves both apelin and GLP-1 and improves glucose tolerance by acting on gut contractions. This study reinforces previous findings demonstrating that HHP processing provides BM with a higher biological value than BM treated by HoP.