-
Biochimica Et Biophysica Acta.... Aug 2017The apelin/apelin receptor system is widely distributed and has a dominant role in cardiovascular homeostasis and disease. The apelin gene is X-linked and is synthesized... (Review)
Review
The apelin/apelin receptor system is widely distributed and has a dominant role in cardiovascular homeostasis and disease. The apelin gene is X-linked and is synthesized as a 77 amino acid pre-pro-peptide that is subsequently cleaved to generate a family of apelin peptides that possess similar functions but display different tissue distribution, potency and receptor binding affinity. Loss-of-function experiments using the apelin and the apelin receptor knockout mice and gain-of-function experiments using apelin peptides have delineated a well-defined role of the apelin axis in cardiovascular physiology and diseases. Activation of the apelin receptor by its cognate peptide ligand, apelin, induces a wide range of physiological effects, including vasodilation, increased myocardial contractility, angiogenesis, and balanced energy metabolism and fluid homeostasis. The apelin/apelin receptor pathway is also implicated in atherosclerosis, hypertension, coronary artery disease, heart failure, diabetes and obesity, making it a promising therapeutic target. Hence, research is expanding to develop novel therapies that inhibit degradation of endogenous apelin peptides or their analogues. Chemical synthesis of stable apelin receptor agonists aims to more efficiently enhance the activation of the apelin system. Targeting the apelin/apelin receptor axis has emerged as a novel therapeutic approach against cardiovascular diseases and an increased understanding of cardiovascular actions of the apelin system will help to develop effective interventions.
Topics: Animals; Apelin; Apelin Receptors; Cardiovascular Diseases; Energy Metabolism; Humans; Mice; Mice, Knockout; Myocardial Contraction; Neovascularization, Physiologic; Signal Transduction
PubMed: 27825851
DOI: 10.1016/j.bbadis.2016.11.007 -
Molecular Biology Reports Feb 2023Apelin, an endogenous ligand for the G protein-coupled receptor APJ, is extensively expressed in various systems, especially the nervous system. This article reviews the... (Review)
Review
Apelin, an endogenous ligand for the G protein-coupled receptor APJ, is extensively expressed in various systems, especially the nervous system. This article reviews the role of apelin/APJ system in neurological diseases. In detail, apelin/APJ system can relieve acute brain injury including subarachnoid hemorrhage, traumatic brain injury, and ischemic stroke. Also, apelin/APJ system has therapeutic effects on chronic neurodegenerative disease models, involving the regulation of neurotrophic factors, neuroendocrine, oxidative stress, neuroinflammation, neuronal apoptosis, and autophagy. In addition, through different routes of administration, apelin/APJ system has a biphasic effect on depression, epilepsy, and pain. However, apelin/APJ system exacerbates the proliferation and invasion of glioblastoma. Thus, apelin/APJ system is expected to be a therapeutic target for the treatment of nervous system diseases.
Topics: Humans; Apelin; Neurodegenerative Diseases; Apelin Receptors; Oxidative Stress; Brain Injuries; Receptors, G-Protein-Coupled
PubMed: 36378421
DOI: 10.1007/s11033-022-08075-9 -
Journal of Neuroinflammation Jun 2022Spinal cord injury (SCI) causes devastating neurological damage, including secondary injuries dominated by neuroinflammation. The role of Apelin, an endogenous ligand...
BACKGROUND
Spinal cord injury (SCI) causes devastating neurological damage, including secondary injuries dominated by neuroinflammation. The role of Apelin, an endogenous ligand that binds the G protein-coupled receptor angiotensin-like receptor 1, in SCI remains unclear. Thus, our aim was to investigate the effects of Apelin in inflammatory responses and activation of endogenous neural stem cells (NSCs) after SCI.
METHODS
Apelin expression was detected in normal and injured rats, and roles of Apelin in primary NSCs were examined. In addition, we used induced pluripotent stem cells (iPSCs) as a carrier to prolong the effective duration of Apelin and evaluate its effects in a rat model of SCI.
RESULTS
Co-immunofluorescence staining suggested that Apelin was expressed in both astrocytes, neurons and microglia. Following SCI, Apelin expression decreased from 1 to 14 d and re-upregulated at 28 d. In vitro, Apelin promoted NSCs proliferation and differentiation into neurons. In vivo, lentiviral-transfected iPSCs were used as a carrier to prolong the effective duration of Apelin. Transplantation of transfected iPSCs in situ immediately after SCI reduced polarization of M1 microglia and A1 astrocytes, facilitated recovery of motor function, and promoted the proliferation and differentiation of endogenous NSCs in rats.
CONCLUSION
Apelin alleviated neuroinflammation and promoted the proliferation and differentiation of endogenous NSCs after SCI, suggesting that it might be a promising target for treatment of SCI.
Topics: Animals; Apelin; Cell Differentiation; Cell Proliferation; Neuroinflammatory Diseases; Rats; Recovery of Function; Spinal Cord; Spinal Cord Injuries
PubMed: 35725619
DOI: 10.1186/s12974-022-02518-7 -
Molecular Biotechnology Mar 2023Apelin receptor (APJ) ligands elabela (ELA) and apelin have divergent distributions and function differently in vitro and in vivo. Whether differences exist in their... (Comparative Study)
Comparative Study
Apelin receptor (APJ) ligands elabela (ELA) and apelin have divergent distributions and function differently in vitro and in vivo. Whether differences exist in their capacity of recruitment of β-arrestins (ARRBs) to APJ remains unknown. The aim of the current study was to investigate the different effects of ELA and apelin on the interaction between APJ and ARRBs in live cells by NanoBiT®. NanoBiT® system is a new technology for studying protein-protein interaction in real-time in live cells, based on the emission of luminescence when two split components of NanoLuc luciferase, large Bit (LgBit) and small Bit (SmBit), complement each other to form an enzymatically active entity. We tagged the APJ and ARRBs with LgBit or SmBit and then evaluated their interactions in transiently transfected HEK293T cells, and determined the signal strength yielded as a result of the interaction. We also investigated the concentration-dependent response of the APJ-ARRB interaction in response to ELA and apelin. Finally, we assessed the effect of F13A, an APJ antagonist which is structurally very similar to apelin-13, on ELA- and apelin-mediated APJ-ARRB interactions. The NanoLuc® luciferase signal was highest in the pair of APJ-LgBit with SmBit-ARRB1 or SmBit-ARRB2. NanoLuc® luciferase signal increased in a concentration-dependent manner from 0.1 nM to 10 μM in response to ELA or apelin. Interestingly, ELA elicited weaker APJ-ARRB interaction signals than apelin. Pre-treatment with F13A potently reduced the APJ-ARRB interaction in response to both ELA and apelin. Our results demonstrated that both ELA and apelin promoted the interaction of APJ and ARRBs in a concentration-dependent manner, and ELA is less efficacious than apelin in inducing the recruitment of ARRBs to APJ, providing a biased functional aspect of ELA vs. apelin at the receptor signaling level. Additionally, ELA and apelin may share the same binding site(s) or pocket(s) at the APJ level.
Topics: Humans; Apelin; Apelin Receptors; beta-Arrestins; Binding Sites; HEK293 Cells
PubMed: 35960440
DOI: 10.1007/s12033-022-00529-6 -
European Review For Medical and... May 2022Gestational diabetes mellitus (GDM) is a type of diabetes that affects from 3.8% to 6.9% of pregnancies worldwide, causing significant mortality and unfavorable...
OBJECTIVE
Gestational diabetes mellitus (GDM) is a type of diabetes that affects from 3.8% to 6.9% of pregnancies worldwide, causing significant mortality and unfavorable obstetric outcomes, such as delivery trauma and macrosomia risk. The fundamental processes of this metabolic disorder that first appeared during pregnancy are still unknown. Tissue hormones, particularly adipokines, have aided in understanding the pathophysiology of numerous disorders in recent years. This study aims to determine if Apelin-13 (APLN-13), Apelin-36 (APLN-36), Elabela (ELA), and nitric oxide (NO) molecules have all a part in the pathophysiology of GDM.
PATIENTS AND METHODS
The study included 30 pregnant control women and 30 pregnant women who had been diagnosed with GDM in the second trimester and whose body mass index and age were compatible with each other. Blood samples were collected from 60 participants during the second trimester (30 control pregnant women and 30 GDM pregnant women) and postpartum (17 controls vs. 14 GDM). In these blood samples, the amounts of APLN-13, APLN-36, ELA, and NO were studied using the ELISA method. In addition, the participants' glucose, lipid profiles, and other parameters were obtained from the hospital record files. At postpartum, 29 pregnant women (13 control and 16 pregnant women with GDM) dropped out of the study without explanation.
RESULTS
In the second trimester and postpartum plasma of mothers with GDM, APLN-13, APLN-36, NO, and ELA molecules were found to be significantly higher (< 0.05), compared to those of the control mothers, while APLN-13, APLN-36, NO values were significantly lower (0.05). While APLN-13, APLN-36, NO amounts in mothers with GDM were positively correlated with glucose amounts, they were negatively correlated with ELA amounts. Similarly, the triglyceride amounts in mothers with GDM were positively correlated with APLN-13, APLN-36 and NO, while they were negatively correlated with the ELA amounts. Due to gestational diabetes, APLN-13, APLN-36, NO, glucose, and triglyceride increased, and ELA decreased.
CONCLUSIONS
It is predicted that the glucose increase in GDM is because Apelins reduce glucose transport to erythrocytes by inhibiting the sodium-dependent glucose transporter (SGLT) and that the increase in triglyceride and NO may be associated with high glucose levels in GDM. As a result, we believe that the above-mentioned chemicals may cause GDM Pathology by triggering one another.
Topics: Apelin; Blood Glucose; Communication; Diabetes, Gestational; Female; Glucose; Humans; Intercellular Signaling Peptides and Proteins; Nitric Oxide; Peptide Hormones; Pregnancy; Triglycerides
PubMed: 35587081
DOI: 10.26355/eurrev_202205_28748 -
Medicine Mar 2021Adipose tissue acts as an active endocrine organ secreting a number of adipokines and may be involved in biological mechanism of stroke. Vaspin, apelin, and visfatin...
Adipose tissue acts as an active endocrine organ secreting a number of adipokines and may be involved in biological mechanism of stroke. Vaspin, apelin, and visfatin play important roles in the regulation of vascular disorders.Our aim was to evaluate whether the concentrations of vaspin, apelin, and visfatin were associated with stroke risk.A total of 235 patients with stroke (156 patients with ischemic stroke and 79 patients with hemorrhagic stroke) and 235 age- and gender-matched healthy controls were included in this study. A sandwich ELISA was developed to measure the serum vaspin, apelin, and visfatin levels.There was a statistically significant difference in the median levels of serum vaspin, apelin, and visfatin levels between stroke cases and controls (vaspin: 1.50 vs 1.07 ng/ml; apelin: 1.56 vs 1.32 pg/ml; visfatin: 23.40 vs 19.65 ng/ml; all P values <.001). Multiple logistic regression analysis showed that, serum vaspin and visfatin levels were significantly inversely associated with increased risk of stroke, and the odds ratios (ORs) in the highest tertile were 2.25 [95% confidence interval (CI) 1.38-3.67; P for trend <.001] for vaspin and 2.56 (95% CI 1.46-4.47; P for trend <.001) for visfatin, respectively, compared with the lowest tertile. Higher apelin levels were marginally associated with lower stroke risk (P for trend =.060).Our study indicated that higher vaspin, apelin, and visfatin levels might be associated with increased stroke risk. Necessary prospective cohort studies should be conducted to confirm this association in the future.
Topics: Adult; Aged; Apelin; Case-Control Studies; China; Female; Hemorrhagic Stroke; Humans; Ischemic Stroke; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Risk Factors; Serpins
PubMed: 33761698
DOI: 10.1097/MD.0000000000025184 -
Archives of Endocrinology and Metabolism Feb 2019In this study, we aimed to evaluate serum irisin and apelin levels in patients with subclinical hypothyroidism (SCH) when they were subclinical hypothyroid and become...
OBJECTIVE
In this study, we aimed to evaluate serum irisin and apelin levels in patients with subclinical hypothyroidism (SCH) when they were subclinical hypothyroid and become euthyroid after levothyroxine therapy and association of these adipokines with markers of atherosclerosis such as serum homocysteine levels and carotid intima-media thickness (IMT).
SUBJECTS AND METHODS
The study included 160 patients with newly diagnosed subclinical hypothyroidism due to Hashimoto's thyroiditis and 86 euthyroid healty subjects. Serum glucose and lipid profile, insulin, HOMA, TSH, free T3, free T4, anti-thyroperoxidase and anti-thyroglobulin antibodies, homocysteine, apelin and irisin levels were measured in all study subjects. Thyroid and carotid ultrasound examinations were performed. The subclinical hypothyroid group was reevaluated after 12-weeks of levothyroxine therapy when they became euthyroid.
RESULTS
Clinical characteristics of the patient and control group were similar. Glucose, insulin and HOMA levels, lipid parameters and free T3 were similar between the two groups.. Serum homocystein was higher and apelin was lower in patients with SCH, but irisin levels were similar between the two groups. While thyroid volume was lower, carotid IMT was significantly greater in patients with SCH (pCarotidIMT:0,01). After 12-weeks of levothyroxine therapy, all the studied parameters remained unchanged except, serum freeT4, TSH, homocystein and apelin. While homocystein decreased (p: 0,001), apelin increased significantly (p = 0,049). In multivariate analysis, low apelin levels significantly contributed to carotid IMT (p = 0,041).
CONCLUSIONS
Apelin-APJ system may play a role in vascular and cardiac dysfunction in patients with SCH and treatment of this condition may improve the risk of cardiovascular disease.
Topics: Adult; Aged; Apelin; Atherosclerosis; Biomarkers; Carotid Intima-Media Thickness; Case-Control Studies; Female; Fibronectins; Hashimoto Disease; Humans; Hypothyroidism; Male; Middle Aged; Prospective Studies; Thyroid Function Tests; Thyroxine; Young Adult
PubMed: 30864627
DOI: 10.20945/2359-3997000000106 -
BMC Ophthalmology Aug 2022Although several clinical studies have analysed the relationship between the levels of vascular endothelial growth factor (VEGF) and apelin-13 in venous blood and...
BACKGROUND
Although several clinical studies have analysed the relationship between the levels of vascular endothelial growth factor (VEGF) and apelin-13 in venous blood and retinopathy of prematurity (ROP), no definitive conclusions have been reached. This study aimed to investigate the relationship between apelin-13 levels and VEGF levels and ROP.
METHODS
Differences in plasma apelin-13 and VEGF levels were analysed in two groups of infants born with birth weight < 1500 g and gestational age < 32 weeks at Peking University People' s Hospital. One group comprised infants diagnosed with ROP and the other group was a control group comprising infants without ROP.
RESULTS
Apelin-13 levels were significantly lower in the ROP group than in the control group, while VEGF levels showed the opposite result (both P < 0.001). Infants with severe ROP had lower apelin-13 levels and higher VEGF levels than with mild ROP (both P < 0.05).The receiver operating characteristic curve for apelin-13 level as the indicator of ROP showed that a cut-off value of 119.6 pg/mL yielded a sensitivity of 84.8% and a specificity of 63.6%, while for VEGF level, the cut-off value of 84.3 pg/mL exhibited a sensitivity of 84.8% and a specificity of 66.7%.
CONCLUSIONS
Plasma apelin-13 and VEGF levels at 4-6 weeks of age may play a role in assisting the diagnosis of ROP.
Topics: Apelin; Case-Control Studies; Gestational Age; Humans; Infant; Infant, Newborn; Infant, Very Low Birth Weight; Retinopathy of Prematurity; Vascular Endothelial Growth Factor A
PubMed: 35953806
DOI: 10.1186/s12886-022-02565-x -
The Journal of Nutrition, Health & Aging 2022Apelin and GDF-15 have been proposed as biomarkers of age-related sarcopenia but evidence in human models is scarce. This study aimed to explore the associations between...
OBJECTIVES
Apelin and GDF-15 have been proposed as biomarkers of age-related sarcopenia but evidence in human models is scarce. This study aimed to explore the associations between blood apelin and GDF-15 with sarcopenia incidence and the evolution of sarcopenia components over two years in older adults >70 years.
DESIGN
Secondary longitudinal analysis of the Multidomain Alzheimer Preventive Trial.
PARTICIPANTS
Older adults (>70 years) attending primary care centers in France and Monaco.
SETTING
Community.
MEASUREMENTS
Serum Apelin (pg/mL) and plasma GDF-15 (pg/mL) were measured. Outcomes included sarcopenia defined by the European Working Group on Sarcopenia in Older People (EWGSOP) and its determinants (appendicular lean mass [ALM] evaluated through a Dual-energy X-ray Absorptiometry (DXA) scan, handgrip strength (HGS) and the 4-meter gait speed) measured over 2 years. Linear mixed models and logistic regression were used to explore the longitudinal associations.
RESULTS
We included 168 subjects from MAPT (median age=76y, IQR=73-79; 78% women). Serum apelin was not significantly associated with sarcopenia incidence (OR=1.001;95%CI=1.000,1.001;p-value>0.05 in full-adjusted models) nor with ALM (β=-5.8E-05;95%CI=-1.0E-04,2.12E-04;p>0.05), HGS (β=-1.1E-04;95%CI=-5.0E-04,2.8E-04;p>0.05), and GS (β=-5.1E-06;95%CI=-1.0E-05,2.0E-05;p>0.05) in fully adjusted models. Similarly, plasma GDF-15 was not associated with both the incidence of sarcopenia (OR=1.001,95%CI=1.000,1.002,p>0.05) and the evolution of its determinants ([ALM, β=2.1E-05;95%CI=-2.6E-04,3.03E-04;p>0.05], HGS [β=-5.9E-04;95%CI=-1.26E-03,8.1E-05; p>0.05] nor GS [β=-2.6E-06;95%CI=-3.0E-05, 2.3E-05;p>0.05]) in fully adjusted models.
CONCLUSIONS
Blood apelin and GDF-15 were not associated with sarcopenia incidence or with the evolution of sarcopenia components over a 2-year follow-up in community-dwelling older adults. Well-powered longitudinal studies are needed to confirm or refute our findings.
Topics: Absorptiometry, Photon; Aged; Alzheimer Disease; Apelin; Clinical Trials as Topic; Female; Growth Differentiation Factor 15; Hand Strength; Humans; Male; Sarcopenia
PubMed: 35718864
DOI: 10.1007/s12603-022-1800-1 -
Acta Biochimica Et Biophysica Sinica Jun 2017Apelin is the endogenous peptide APJ receptor, while APJ is a member of the G protein-coupled receptors family. Recent evidence strongly suggests that Apelin/APJ system... (Review)
Review
Apelin is the endogenous peptide APJ receptor, while APJ is a member of the G protein-coupled receptors family. Recent evidence strongly suggests that Apelin/APJ system influences apoptosis in various diseases through different signal pathways. In this review, we discuss the possible mechanisms by which the Apelin/APJ system inhibits apoptosis, including the phosphatidylinositol-3-kinase (PI3K)/Akt, ERK1/2, caspase signaling, and autophagy pathway. We also summarize the role of Apelin/APJ system in apoptosis in myocardial ischemia-reperfusion (I/R) injury, pulmonary artery hypertension, retinal neovascular disease, acute renal injury, skeletal homeostasis, and gastrointestinal diseases. Apelin/APJ system decreases myocardial infarction size and alleviates myocardial I/R injury by inhibiting cardiomyocytes apoptosis. However, Apelin/APJ system improves pulmonary artery hypertension via increasing apoptosis. Apelin/APJ system exerts neuroprotective effect by blocking apoptosis and participates in the recovery of retinal neovascular disease by suppressing apoptosis. Apelin/APJ system also shows anti-apoptotic effect against acute renal injury and plays a role in regulating skeletal homeostasis. In gastrointestinal disease, Apelin/APJ system plays a potential physiological role in gastrointestinal cytoprotection by regulating apoptosis. We hope that a better understanding of the Apelin/APJ system will help to discover new disease pathogenesis and find possible therapeutic targets of the Apelin/APJ system essential for various diseases.
Topics: Acute Kidney Injury; Animals; Apelin; Apelin Receptors; Apoptosis; Autophagy; Humans; Models, Biological; Myocardial Reperfusion Injury; Signal Transduction
PubMed: 28407045
DOI: 10.1093/abbs/gmx035