Serum Apelin Research Articles

Association of brain natriuretic peptide gene polymorphisms with chronic obstructive pulmonary disease complicated with pulmonary hypertension and its mechanism.

Objective: To examine the association between brain natriuretic peptide (BNP) gene single nucleotide polymorphisms (SNPs) and chronic obstructive pulmonary disease (COPD) and COPD with pulmonary hypertension (PH) and to analyze its mechanism. Methods: The genotypes of BNP at the rs198389, rs6668352, and rs198388 loci in 339 patients with COPD (205 in the COPD/PH− group and 134 in the COPD/PH+ group) and 125 healthy subjects were detected by PCR/Sanger sequencing. The serum levels of BNP, fibrinogen (Fbg), and Apelin were measured in all subjects by ELISA. Results: The BNP rs198389 locus G allele, rs6668352 locus A allele, and 198388 locus T allele were high risk factors for COPD (P<0.001). Logistics regression analysis showed that BNP rs198389 locus G allele, rs6668352 locus A allele, and rs198388 locus T allele were high risk factors for PH in COPD patients (all P<0.001). The levels of the serum BNP and Fbg protein in the control group, COPD/PH− group, and COPD/PH+ group increased successively, and the expression levels of Apelin protein decreased successively (all P<0.001). The BNP and Fbg protein levels in the wild-type, heterozygote, and mutant homozygote in BNP rs198389, rs6668352, and rs198388 loci increased successively, and the serum Apelin protein levels decreased successively (all P<0.001). Conclusion: The polymorphisms of BNP at the rs198389, rs6668352, and rs198388 loci are associated with the occurrence of COPD and COPD with PH, and the occurrence may be related to the abnormal expression level of BNP, Fbg, and Apelin protein in the serum.

Evaluation of Apelin Level in Type 2 Diabetic Patients with Peripheral Neuropathy and Nephropathy

AbstractBackground: Diabetic Peripheral Neuropathy (DPN) and Diabetic Nephropathy (DN) are serious complications of diabetes mellitus. Their pathogenesis is associated with dura-tion of diabetes, hyperglycemia and increased pro-inflammatory response that cause endothelial dysfunction and impaired angiogenesis. Apelin is an endogenous peptide which is expressed in the kidney, adipose tissue, liver, endothelium, and plasma. It contributes to endothelial dysfunction, angio-genesis, and inflammation that lead to pathogenesis of DPN and DN.Aim of Work: To assess serum apelin level in type 2 diabetic patients with peripheral neuropathy and nephropathy.Patients and Methods: 80 subjects were selected from Nasser Institute for Research and divided into four groups: Group 1 included 20 healthy controls, group 2 included 20 diabetic patients without complications, group 3 included 20 patients with DPN and group 4 included 20 patients with DN. They were subjected to monofilament test, fasting blood glucose, kidney function tests, HbA1c, lipid profile, liver profile, urine analysis, urinary albumin/creatinine ratio and serum apelin.Results: Apelin levels are significantly higher in diabetic patients in the presence of neuropathy and nephropathy compared to other groups. There was a positive correlation between serum apelin and HbA1c in group 2 and 3. Further, there was a positive correlation between apelin level and HbA1c, serum creatinine and urine albumin/creatinine ratio in group 4. There was no correlation between serum apelin and other parameters in all studied groups.Conclusion: Serum apelin may play an important role in pathogenesis of DPN and DN.

Apelin: A novel prognostic predictor for atrial fibrillation recurrence after pulmonary vein isolation.

Apelin, the ligand for the APJ receptor, is involved in the pathogenesis of atrial fibrillation (AF). However, whether serum apelin can predict the recurrence of AF after pulmonary vein isolation (PVI) has not been determined.A prospective cohort study was performed in patients with AF (but without structural heart disease) who were undergoing first-time PVI. Serum apelin-12 was measured by enzyme-linked immunosorbent assay. Echocardiographic examination was performed at baseline, 3 months, and 6 months after PVI. Patients were followed up for 6 months after PVI, and the association between baseline apelin-12 and AF recurrence (early recurrence: within 3 months after ablation; late recurrence: 3–6 months after ablation) was analyzed.A total of 61 patients were included in the study. Baseline serum level of apelin-12 was significant lower in patients with early (median [interquartile range]: 1844 [1607–2061] vs 2197 [1895–2455] ng/L, P = .01) and late (1639 [1524–1853] vs 1923 [1741–2303] ng/L, P = .02) AF recurrence compared with patients without these events. Results of Cox stepwise multivariate analysis demonstrated that lower baseline apelin-12 (<2265 ng/L) was independently associated with increased AF recurrence within 6 months after PVI (P < .05). The specificity and positive predictive value of apelin-12 for AF recurrence were significantly higher than those of baseline N-terminal brain proBNP (60.4% vs 28.6%, P < .001; 58.8% vs 34.4%, P = .01), although the sensitivity and negative predictive value were similar.Reduced baseline serum apelin-12 may be an independent risk factor for the recurrence of AF after PVI in patients without structural heart disease.

Inhibitory Regulation of Skin Fibrosis in Systemic Sclerosis by Apelin/APJ Signaling.

Apelin/APJ signaling has been determined to regulate cardiac and arterial fibrosis and to be involved in the pathogenesis of pulmonary arterial hypertension. Our objective was to elucidate the role of apelin in skin fibrosis in systemic sclerosis (SSc). Expression of apelin/APJ in normal and SSc fibroblasts was compared. Effects of small interfering RNA depletion and the addition of apelin in fibroblasts were analyzed. The effect of apelin injections on bleomycin-induced dermal fibrosis in mice was investigated. We analyzed the effects of the biased agonist of APJ, MM07, on skin fibrosis in vitro and in vivo. The expression of apelin in SSc fibroblasts was significantly lower than that in normal fibroblasts. Serum apelin levels were negatively correlated with the modified Rodnan skin thickness score in SSc patients. Stimulation with transforming growth factor β1 (TGFβ1) inhibited apelin expression in fibroblasts, suggesting that activation of TGFβ1 signaling in SSc might be responsible for reduced apelin expression in SSc fibroblasts. Small interfering RNA depletion of apelin from fibroblasts significantly enhanced fibrosis-related gene expression, and treatment with apelin protein significantly inhibited TGFβ1 signaling in fibroblasts. Administration of apelin significantly inhibited bleomycin-induced dermal fibrosis in mice. We demonstrated that MM07 had greater potential than apelin to inhibit fibrosis in vivo and in vitro. Collectively, TGFβ1 signaling and apelin signaling may counteract each other in the fibrotic process of SSc. Inhibitory regulation of TGFβ1-induced skin fibrosis by apelin/APJ signaling may be involved in the pathogenesis of SSc and could be a therapeutic target for fibrosis in SSc patients.

Serum Apelin and Obesity-Related Complications in Egyptian Children.

BACKGROUND:The rapidly increasing prevalence of childhood obesity became a major burden on health worldwide, giving an alarm to clinicians and researchers. Adipocytes act as an active endocrine organ by releasing plenty of bioactive mediators (adipokines) that play a major role in regulating metabolic processes. Apelin is a recently identified adipokine that is expressed in adipocytes.AIM:The current work aimed to uncover the relation between serum apelin and childhood obesity and its related complications as hypertension and hyperglycemiaMETHOD:A group of 50 obese and 31 non-obese; sex- and age-matched children were enrolled in our study with a mean age of (9.5 ± 2.1) and (8.7 ± 1.3) respectively. Anthropometric measurements, blood pressure, were assessed in all studied participants, we also determined the lipid profile, serum insulin, fasting blood glucose (FBG) level, HOMA-IR and serum apelin.RESULTS:Obese children had higher levels of HbA1c, FBG, serum insulin, HOMA-IR, total cholesterol, triglycerides, low-density lipoprotein (LDL) and diastolic blood pressure (DBP Z-score); compared to controls (all P < 0.05). Apelin was significantly higher in obese children versus controls and correlated positively with BMI Z-Score (P = 0.008), DBP Z-Score (P = 0.02), cholesterol, TG (both P = 0.02), serum insulin (P = 0.003), FBG and HOMA-IR (both P = 0.001). Linear regression analysis showed that FBG was the most effective factor in predicting the level of serum apelin (P = 0.04).CONCLUSION:This work supports the hypothesis that apelin may have a crucial role in the pathogenesis of health hazards related to obesity in children including insulin resistance, hypertension and a higher risk of occurrence of metabolic syndrome.

Oxidative stress contribution to attention deficit hyperactivity disorder in children with epilepsy

Children with epilepsy have a high incidence of attention deficit hyperactivity disorder (ADHD). Oxidation stress and disturbed neurotransmitters are suggested mechanisms; however, their role is not fully explored. This study evaluates the association between circulating malondialdehyde as an oxidation stress marker, apelin neuropeptide, and ADHD in children with epilepsy. Fifty children with epilepsy of unknown etiology, of which 25 have ADHD, as well as 35 healthy children were included. Serum levels of malondialdehyde and apelin were estimated. We investigated the association between seizure severity, response to medications, malondialdehyde, apelin levels, and ADHD in children with epilepsy. Serum malondialdehyde and apelin levels were higher in children with epilepsy, especially those with ADHD. Malondialdehyde and apelin levels have significant positive correlation with the Chalfont Seizure Severity Score. Regression analysis showed that elevated malondialdehyde is an independent risk factor for ADHD in children with epilepsy (OR: 1.401, 95%CI: 1.056–1.859, p= 0.02). No significant association was found between malondialdehyde and apelin levels and the type of epilepsy or ADHD. Longer duration of epilepsy, increased seizure severity, and uncontrolled seizures are associated with increased oxidation stress, which further increased susceptibility for ADHD. In spite of elevated apelin in children with ADHD, the elevation did not increase the risk of ADHD in children with epilepsy.

ROLE OF APELIN/MONOCYTE CHEMOATTRACTANT PROTEIN-1, INFLAMMATORY, APOPTOTIC MARKERS IN THE REGULATION OF PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE

Objective: The objective of this study is to investigate blood nuclear factor κB (NF-κB), apelin, Lipid peroxide product ; thiobarbituric acid (TBA) malonaldehyde (MDA), monocyte chemoattractant protein-1 (MCP-1), B-cell lymphoma 2 (Bcl2), and paraoxonase (PON1) levels in patients with non -alcoholic fatty liver disease (NAFLD) in a trail to correlate the significance of these biomarkers in the diagnosis and initiation of NAFLD patients.Methods: A total of 32 patients with NAFLD and 45 healthy controls were enrolled in the study. Apelin levels were measured along with, NF-κB, MCP1, MDA, Bcl2, and PON1 were detected.Results: Significant increase in serum NF-κB, MDA, MCP1, and apelin levels in NAFLD patients with percentages increase 1031.23, 293.02, 165.93, and 120 %, respectively, while significant reduction in PON1 and BCl2 with percentages decrease 54.58 and 79.03 %, respectively, were detected as compared to controls. A significant correlation was found between serum concentration of the measured biomarkers with the incidence of NAFLD.Conclusions: It could be concluded that the patients with NAFLD have significantly increased circulating apelin, NF-κB, and MDA levels as compared to healthy control subjects while significant reduction in BCl2 and PON1 levels were recorded. Besides, the NAFLD status is tightly attributed to the existence of insulin resistance and oxidative stress.

Evaluation of Serum Apelin-13 in Acne Vulgaris Patients

Acne is a longstanding inflammatory disease of the pilosebaceous unit resulting from androgen-induced increased sebum production, altered keratinization, inflammation, and bacterial colonization of hair follicles by Propionibacterium acne [1]. Apelin is a newely discovered adipocytokine secreted by white adipose tissue and couples with the APJ receptor with the highest affinity. Apelin and the APJ receptor are found in pancreatic islet cells and found to have a role in energy metabolism. Many researches show that apelin has a role in glucose homeostasis regulation, insulin secretion, and increasing insulin sensitivity [2].The aim of the work was to evaluate the serum level of Apelin-13 in patients with acne vulgaris .Serum apelin was measured in 40 patients with moderate to severe acne vulgaris and 30 healthy controls using enzyme-linked immunosorbent assay (ELISA). Serumlevels of apelin13 in patients with acne vulgaris was found to be higher than in healthy controls (p value <0.005).In Conclusion Serum apelin13 has a role in the pathophysiology of acne vulgaris patients.

Protective effects of troxerutin on maternal high-fat diet-induced impairments of spatial memory and apelin in the male offspring.

Objective(s):Maternal high-fat diet (HFD) is linked with metabolic and cognitive deficits in offspring. Neuroprotective effects of troxerutin, a natural bioflavonoid, have been reported recently. This study aimed to investigate the effects of troxerutin on spatial memory and serum and hippocampal apelin levels in the male offspring of HFD fed mothers.Materials and Methods:Three-week-old female Wistar rats (n= 40) received HFD or control diet (CD) for 8 weeks. After mating, pregnant animals were divided into two subgroups according to the troxerutin (TRO) supplementation: CD, CD+TRO, HFD, and HFD+TRO. HFD continued to the end of lactation in HFD and HFD+TRO groups. TRO was gavaged (150 mg/kg/day) during pregnancy. After weaning, the male offspring were fed a normal diet until 12 weeks of age. Spatial memory was evaluated in the Morris water maze (MWM) on postnatal day (PND) 90. Total apelin concentration was measured in the serum of maternal rats before mating and after lactation and also in the serum and hippocampus of their male offspring.Results:Both traveled distance (P<0.05) and time spent (P<0.05) in the target quadrant were significantly decreased in the offspring of HFD-fed dams, which were reversed by TRO treatment. Moreover, TRO significantly (P<0.05) decreased serum apelin levels in dams. Furthermore, TRO treatment in dams significantly (P<0.05) increased serum and hippocampal levels of apelin in their offspring.Conclusion:These results indicated that TRO treatment during pregnancy improved maternal HFD-induced spatial memory impairments of the offspring possibly through modulation of serum and hippocampal apelin levels.

Vitamin D supplementation and inflammatory and metabolic biomarkers in patients with knee osteoarthritis: post hoc analysis of a randomised controlled trial.

The aim of this study was to determine whether vitamin D supplementation and maintaining vitamin D sufficiency are associated with changes in inflammatory and metabolic biomarkers in patients with knee osteoarthritis (OA) and vitamin D deficiency. A total of 413 participants with symptomatic knee OA and vitamin D deficiency were enrolled in a randomised, placebo-controlled trial and received 1·25 mg vitamin D3 or placebo monthly for 24 months across two sites. In this post hoc analysis, 200 participants from one site (ninety-four from the placebo group and 106 from the vitamin D group; mean age 63·1 (sd 7·3) years, 53·3 % women) were randomly selected for measurement of serum levels of inflammatory and metabolic biomarkers at baseline and 24 months using immunoassays. In addition, participants were classified into two groups according to serum 25-hydroxyvitamin D (25(OH)D) levels at months 3 and 24: (1) not consistently sufficient (25(OH)D≤50 nmol/l at either month 3 or 24, n 61), and (2) consistently sufficient (25(OH)D>50 nmol/l at both months 3 and 24, n 139). Compared with placebo, vitamin D supplementation had no significant effect on change in serum high-sensitive C-reactive protein, IL-6, IL-8, IL-10, leptin, adiponectin, resistin, adipsin and apelin. Being consistently vitamin D sufficient over 2 years was also not associated with changes in these biomarkers compared with not being consistently sufficient. Vitamin D supplementation and maintaining vitamin D sufficiency did not alter serum levels of inflammatory and metabolic biomarkers over 2 years in knee OA patients who were vitamin D insufficient, suggesting that they may not affect systemic inflammation in knee OA patients.

DUNALIELLA SALINA IMPROVED OBESITY-ASSOCIATED INFLAMMATION AND OXIDATIVE DAMAGE IN ANIMALS’ RODENT

Objective: The objective of this study is to investigate the efficacy of microalgae Dunaliella salina to improve apelin, oxidative damage, inflammatory, and apoptotic function implicated in high-fat diet (HFD)-induced obesity in rats.Methods: Fifty male Westar albino rats weighing 150–160 g were fed on HFD for 12 weeks. Treatment of obese rats with D. salina was carried out in a dose 150 mg/kg body weight as compared to orlistat as anti-obesity standard drug. Blood nuclear factor kappa-B cells (NF-kB), apelin, apoptosis regulator (B-cell lymphoma 2 [BCl2]), monocytes chemo attractant protein-1, paraoxonase-1 (PON1) were determined in serum of different groups. Besides, lipid peroxidation (malondialdehyde [MDA]), glutathione (GSH) levels as well as histopathological examination were investigated in liver tissue of obese rats.Results: Serum apelin, MDA, and NF-kB levels were significantly high, reached to 97.25, 158.18, 511.433, and 170.73%, respectively. While significant decrease in PON1 (47.82%), BCl2 (74.88%), and GSH (63.54 %), levels were detected in the obese rats compared to controls. Obviously improvement in all biomarkers under investigation upon treated obese rats with ethanol extract of D. salina. Histopathological examination of obese hepatic tissue showed dilatation in the central portal veins associated with inflammatory cells infiltration in the portal area and congestion. However, treatment of obese rats with D. salina confirmed biochemical analysis and declared less diffuse inflammatory cells infiltration as well as less focal infiltration in both hepatic parenchyma and portal area with higher improvement in D. salina than drug.Conclusion: It could be concluded that D. salina has a great ability to improve inflammation associated with obesity as well as damaged hepatic architectures which can be used as a promising anti-obesity nutraceuticals.

The Relationship between Serum Apelin Levels and the Severity of Calcific Aortic Stenosis.

Apelin, an endogenous peptide, has recently gained attention due to its positive inotropic effects in heart failure physiopathology. We investigated the relationship between serum apelin levels and the severity of calcific aortic stenosis (AS). A total of 68 consecutive patients diagnosed with calcific AS and a control group of 32 subjects were included in the study. The subjects were divided into three group as follows: the control group, the mild-moderate AS group and the severe AS group. Blood samples were obtained from all of the subjects, which were used for biochemical comparisons of apelin 36 and high-sensitive C-reactive protein (hsCRP) levels. Plasma apelin 36 levels were significantly lower in the patients with severe AS [490 (247-1074) pg/ml] compared to both the mild-moderate AS [209 (97-453) pg/ml] and control [660 (378-1200) pg/ml] groups (p < 0.001). Correlation analysis between the left ventricular mass index and apelin concentrations revealed a significant negative correlation between the two parameters (p < 0.001, r = -0.478). Our study demonstrated decreased apelin levels and increased hsCRP concentrations in patients with severe calcific AS. Our findings may help to clarify the exact pathophysiologic role of apelin in cardiovascular diseases.

Serum adipokine (apelin) in lean and obese polycystic ovary syndrome patients before and after metformin treatment

Abstract Background Polycystic ovary syndrome (PCOS) is a common disorder in the childbearing period. Apelin is a regulator of glucose metabolism and is associated with insulin resistance (IR). Metformin is used in PCOS, but its effects on serum apelin in PCOS patients are unknown. Aim To compare serum apelin levels in lean and obese PCOS women and to evaluate the effects of metformin treatment on serum apelin levels, clinical and metabolic parameters, and hormone profile in these patients. Methods A prospective interventional study involving 59 PCOS patients (38 obese and 21 lean) was conducted. Body mass index (BMI), serum apelin, glucose, insulin, FSH, LH and testosterone levels were measured, and HOMA-IR was calculated before and after six months of metformin treatment. Results Significantly higher BMI and serum apelin (P Conclusion Serum apelin levels were higher in obese than lean PCOS patients. Metformin treatment improved insulin sensitivity and decreased serum apelin, LH and testosterone levels in both groups; lean PCOS patients showed better response to metformin treatment.

Prognostic Value of Serum Apelin Level in Children with Heart Failure Secondary to Congenital Heart Disease.

Apelin is an endogenous inotrope that decreased in heart failure (HF). We aimed to evaluate the prognostic value of its level in children with HF due to congenital heart disease (CHD). Sixty children with HF due to CHD were included as a patient group. Sixty healthy children matched for age, sex, and weight served as a control group. Chest X-ray, electrocardiogram (ECG), echocardiography, andlaboratory investigations such as complete blood count, c-reactive protein, and serum apelin levels were performed for all included children at admission. All children were followed up for 3 months. Serum apelin level was significantly decreased in patients with HF at admissionthan healthy control group andthis decrease went with advanced stage of HF. Serum apelin levels were significantly decreased in patients with unfavorable prognosisthan those with favorable prognosis. At acutoff lower than 126ng/l, the sensitivity of serum apelin to predict unfavorable prognosis in children with HF was 96% with a specificity of 82%. Serum apelin level had a significant positive correlation with left ventricular systolic function (P < 0.05). Moreover, it had a significant negative correlation with heart rate, respiratory rate, Ross classification, c-reactive protein, cardiothoracic ratio, and bothleft and right ventricular dimensions (P < 0.05). Serum apelin level has a good predictive value for adverse outcome in children with HF due to CHD.

Serum Apelin: A New Marker of Early Atherosclerosis in Children with Type 1 Diabetes Mellitus.

INTRODUCTION:Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases in children that may be complicated by micro or macrovascular complications. Measurement of the carotid intima-media thickness (CIMT) allows the early detection of atherosclerotic alterations of blood vessels that may complicate T1DM.SUBJECTS AND METHODS:This study is a case-control study. Participants were classified into two groups. The first group included 40 children with T1DM and the second group included 30 matched healthy controls. The studied cases were recruited from Endocrinology and Diabetology Unit, Pediatric Hospital, Ain Shams University. Serum apelin, cholesterol, TG, LDL were measured for every case. Also, albumin level was analyzed in urine. Measurement of the carotid intima-media thickness (CIMT) was done for all cases.RESULTS:Comparison between T1DM patients and controls revealed that serum apelin, cholesterol, TG, LDL and albuminuria were significantly increased in cases compared to controls. Significant positive correlations were detected between HbA1C, albuminuria and lipid profile with apelin in the diabetic group (p < 0.05). CIMT has significant positive correlation with serum apelin levels (r = 0.36, p = 0.05). Also, this study found positive correlations between CIMT and some variables as LDL, SBP z-score and duration of the illness.CONCLUSION:Increased levels of serum apelin in T1DM patients may be considered as predicting factor for the ongoing development of vascular sequels. This study highlighted the possible validity of apelin assay as an early predictor of atherosclerosis in T1DM children. Evaluating CIMT in these patients is of at most important for early detection of subclinical atherosclerosis.

Effects of two Exercise Modalities of Sprint Interval Training and Combined Training (Strength-Aerobic) on Serum Apelin levels and Insulin Resistance in Women with Type 2 Diabetes

Effects of two Exercise Modalities of Sprint Interval Training and Combined Training (Strength-Aerobic) on Serum Apelin levels and Insulin Resistance in Women with Type 2 Diabetes

Apelin impairs myogenic response to induce diabetic nephropathy in mice.

The cause of the invalid reaction of smooth muscle cells to mechanical stimulation that results in a dysfunctional myogenic response that mediates the disruption of renal blood flow (RBF) in patients with diabetes is debatable. The present study revealed that increased apelin concentration in serum of diabetic mice neutralized the myogenic response mediated by apelin receptor (APJ) and resulted in increased RBF, which promoted the progression of diabetic nephropathy. The results showed that apelin concentration, RBF, and albuminuria:creatinine ratio were all increased in kkAy mice, and increased RBF correlated positively with serum apelin both in C57 and diabetic mice. The increased RBF was accompanied by decreased phosphorylation of myosin light chain (MLC), β-arrestin, and increased endothelial NOS in glomeruli. Meanwhile, calcium, phosphorylation of MLC, and β-arrestin were decreased by high glucose and apelin treatment in cultured smooth muscle cells, as well. eNOS was increased by high glucose and increased by apelin in cultured endothelial cells (ECs). Knockdown of β-arrestin expression in smooth muscle cells cancelled phosphorylation of MLC induced by apelin. Therefore, apelin may induce the progression of diabetic nephropathy by counteracting the myogenic response in smooth muscle cells.-Zhang, J., Yin, J., Wang, Y., Li, B., Zeng, X. Apelin impairs myogenic response to induce diabetic nephropathy in mice.

Is serum apelin related to portal hemodynamics in patients with liver cirrhosis?

BackgroundApelin is the endogenous ligand of the angiotensin-like receptor. The expression of apelin–APJ (apelin receptor) signaling is associated with the development of portal hypertension (PH) and contributes toward the formation of Porto systemic collaterals and splanchnic neovascularization in PH.AimsWe aimed to study the relationship between apelin and portal hemodynamics in cirrhotic patients.Patients and methodsThus study included 60 cirrhotic patients from Menoufia University Hospitals (Egypt) and 20 healthy volunteers as a control group. Participants underwent a physical examination and laboratory investigations [complete blood count, urea, creatinine, alanine transaminase, aspartate transaminase (AST), serum albumin, bilirubin, international normalized ratio, hepatitis C virus antibody, hepatitis B virus antigen, hepatitis C virus PCR, alpha feto protein (AFP), and serum level of apelin]. Abdominal ultrasonographic studies of portal vein diameter, splenic size, and portal hemodynamics were carried out for all participants. Child–Pugh score, model for end-stage liver disease score, and AST/platelet (PLT) index were calculated for all participants.ResultsSerum apelin was highly significantly elevated in cirrhotics than in controls, with a P value of 0.001. Serum apelin was significantly correlated to some laboratory parameters in cirrhotics such as PLT count, alanine transaminase, AST, γ-glutamyl transferase, and bilirubin, with P value less than 0.05. There was a positive correlation between serum apelin level and the degree of liver fibrosis estimated by the AST/PLT index. Serum apelin was significantly correlated to portal vein diameter and portal flow velocity, with a P value less than 0.05, and highly significantly correlated to splenomegaly, with a P value of 0.001. The optimal cut-off point of serum apelin for the prediction of PH in cirrhotics is 2550 ng/dl, with a sensitivity of 89%, a specificity of 65%, and an accuracy of 81%.ConclusionSerum apelin is elevated in patients with cirrhosis and PH, and a positive correlation is found between serum apelin and the degree of hepatic fibrosis. Measurement of serum apelin represents a rapid, noninvasive method for the prediction of PH in cirrhotics and can assess the degree of hepatic fibrosis.

Relations of Apelin with Cardiac Remodeling in Patients with Hypertension and Type 2 Diabetes.

The peptide apelin has antihypertensive and antidiabetic properties, but its role in the processes of cardiac remodeling in patients with hypertension and type 2 diabetes (T2D) is poorly understood. The aim of the study was to investigate apelin levels in patients with hyper-tension and T2D and to determine its relations to heart structural parameters and types of cardiac remodeling. We examined 63 patients with hypertension and T2D. Investigation complex included physical examination, standard transthoracic echocardiography and determination of apelin serum levels by ELISA. Control group consisted of 16 volunteers. The apelin levels in patients were significantly lower than those in volunteers (0.882(0.788; 0.924) ng/ml versus 1.097(0.944; 1.171) ng/ml, p<0.001). Negative correlation relations of apelin with septal wall thickness (r=-0.50, p<0.001), posterior wall thickness (r=-0.46, p<0.001), left ventricle (LV) mass (r=-0.39, p<0.01), LV mass index (r=-0.42, p<0.001) and left atrium size (r=-0.45, p<0.001) were found. In patients with concentric remodeling of LV apelin levels were 0.918 (0.892; 0.984) ng/ml, with concentric LV hypertrophy - 0.855(0.722; 0.899) ng/ml, with eccentric LV hypertrophy - 0.884(0.856; 0.929) ng/ml (p<0.05, p<0.001, p<0.001 versus control, respectively). Patients with concentric LV hypertrophy had significantly lower apelin levels than patients with concentric remodeling of LV (p<0.05). Patients with hypertension and T2D have significant reduction of apelin blood levels, which is accompanied by cardiac remodeling development primarily concentric LV hypertrophy and have negative correlation relations of apelin with heart structural parameters that characterize LV remodeling and left atrium size.

Effect of L-Carnitine Supplementation on Apelin and Apelin Receptor (Apj) Expression in Cardiac Muscle of Obese Diabetic Rats.

Objective L-carnitine (LC) has been shown to protect cardiac metabolism in diabetes patients with cardiovascular diseases (CVDs). Apelin, a newly discovered adipocytokines, is an important regulator of cardiac muscle function; however, the role of the level of expression of Apelin axis in improvement of cardiac function by LC in diabetic patients, is not clear. In the present study, obese insulin-resistant rats were used to determine the effect of LC, when given orally with a high-calorie diet, on Apelin and Apelin receptor (Apj) expression in cardiac muscle. Materials and Methods In this experimental study, rats were fed with high-fat/high-carbohydrate diet for five weeks and subsequently were injected with streptozotocin 30 mg/kg for induction of obesity and insulin resistance. After confirming the induction of diabetes (serum glucose above 7.5 mmol/L), the animals received LC 300 mg/kg in drinking water for 28 days. On days 0, 14 and 28 after treatment, cardiac Apelin and Apj gene expression was evaluated by real time polymerase chain reaction (PCR) analysis. Serum levels of insulin, Apelin, glucose, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and the homeostasis model assessment of insulin resistance (HOMA-IR) were also measured using commercial kits. Results Cardiac Apelin and Apj expression and serum Apelin were increased in obese rats, while LC supplementation decreased the serum levels of Apelin and down-regulated Apelin and Apj expression in cardiac muscle. These changes were associated with reduced insulin resistance markers and serum inflammatory factors and improved lipid profile. ConclusionWe concluded that LC supplementation could attenuate the over-expression of Apelin axis in heart of diabetic rats, a novel mechanism by which LC improves cardiovascular complications in diabetic patients.