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International Immunopharmacology Aug 2022Apelin, an endogenous ligand for the G protein-coupled receptor (APJ), is widely distributed within the central nervous system and diverse organs in human and animals.... (Review)
Review
Apelin, an endogenous ligand for the G protein-coupled receptor (APJ), is widely distributed within the central nervous system and diverse organs in human and animals. Recent studies indicate that the apelin/APJ system plays an important role in physiological and pathophysiological situations. Apelin/APJ could inhibit inflammatory response by down-regulation of the nuclear factor-κB (NF-κB) pathway and by up-regulation of the extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathway etc. Basic and preliminary research demonstrated that apelin/APJ system was involved in multiple diseases such as cardiovascular system diseases, liver and kidney diseases, neurological diseases, inflammatory intestinal diseases, pancreatitis, lung injury, aging, and obesity. Further, deficiency or overabundance of apelin can aggravate disease states in that inflammation is not only an important physiologic defense mechanism but also a potential mediator of organ damage. In this review, we summarize recent apelin/APJ system research progress with emphasis on the influence of the system on inflammation. Further, the mechanistic basis by which apelin regulates various inflammation-related diseases is analyzed. Finally, apelin and APJ might be presented as potential therapeutic targets for treatment of diseases mediated or exacerbated by inflammation.
Topics: Animals; Apelin; Apelin Receptors; Inflammation; Ligands; Receptors, G-Protein-Coupled
PubMed: 35605524
DOI: 10.1016/j.intimp.2022.108822 -
Nature Medicine Sep 2018Sarcopenia, the degenerative loss of skeletal muscle mass, quality and strength, lacks early diagnostic tools and new therapeutic strategies to prevent the... (Randomized Controlled Trial)
Randomized Controlled Trial
Sarcopenia, the degenerative loss of skeletal muscle mass, quality and strength, lacks early diagnostic tools and new therapeutic strategies to prevent the frailty-to-disability transition often responsible for the medical institutionalization of elderly individuals. Herein we report that production of the endogenous peptide apelin, induced by muscle contraction, is reduced in an age-dependent manner in humans and rodents and is positively associated with the beneficial effects of exercise in older persons. Mice deficient in either apelin or its receptor (APLNR) presented dramatic alterations in muscle function with increasing age. Various strategies that restored apelin signaling during aging further demonstrated that this peptide considerably enhanced muscle function by triggering mitochondriogenesis, autophagy and anti-inflammatory pathways in myofibers as well as enhancing the regenerative capacity by targeting muscle stem cells. Taken together, these findings revealed positive regulatory feedback between physical activity, apelin and muscle function and identified apelin both as a tool for diagnosis of early sarcopenia and as the target of an innovative pharmacological strategy to prevent age-associated muscle weakness and restore physical autonomy.
Topics: Adenylate Kinase; Adolescent; Adult; Aged; Aged, 80 and over; Aging; Animals; Apelin; Apelin Receptors; Body Weight; Exercise; Humans; Kinetics; Mice, Inbred C57BL; Muscle Cells; Muscle Weakness; Muscle, Skeletal; Organelle Biogenesis; Protein Biosynthesis; Proto-Oncogene Proteins c-akt; Regeneration; Ribosomal Protein S6 Kinases, 70-kDa; Sarcopenia; Satellite Cells, Skeletal Muscle
PubMed: 30061698
DOI: 10.1038/s41591-018-0131-6 -
European Journal of Pharmacology Jun 2023Heart failure is one of the most significant public health problems faced by millions of medical researchers worldwide. And pathological cardiac hypertrophy is... (Review)
Review
Heart failure is one of the most significant public health problems faced by millions of medical researchers worldwide. And pathological cardiac hypertrophy is considered one of the possible factors of increasing the risk of heart failure. Here, we introduce apelin/ELABELA-APJ system as a novel therapeutic target for cardiac hypertrophy, bringing about new directions in clinical treatment. Apelin has been proven to regulate cardiac hypertrophy through various pathways. And an increasing number of studies on ELABELA, the newly discovered endogenous ligand, suggest it can alleviate cardiac hypertrophy through mechanisms similar or different to apelin. In this review, we elaborate on the role that apelin/ELABELA-APJ system plays in cardiac hypertrophy and the intricate mechanisms that apelin/ELABELA-APJ affect cardiac hypertrophy. We also illuminate and make comparisons of the newly designed peptides and small molecules as agonists and antagonists for APJ, updating the breakthroughs in this field.
Topics: Humans; Apelin; Apelin Receptors; Cardiomegaly; Heart Failure; Receptors, G-Protein-Coupled
PubMed: 37062502
DOI: 10.1016/j.ejphar.2023.175727 -
Cardiovascular Research Dec 2023Cardiovascular disease is the leading cause of death worldwide. Its prevalence is rising due to ageing populations and the increasing incidence of diseases such as... (Review)
Review
Cardiovascular disease is the leading cause of death worldwide. Its prevalence is rising due to ageing populations and the increasing incidence of diseases such as chronic kidney disease, obesity, and diabetes that are associated with elevated cardiovascular risk. Despite currently available treatments, there remains a huge burden of cardiovascular disease-associated morbidity for patients and healthcare systems, and newer treatments are needed. The apelin system, comprising the apelin receptor and its two endogenous ligands apelin and elabela, is a broad regulator of physiology that opposes the actions of the renin-angiotensin and vasopressin systems. Activation of the apelin receptor promotes endothelium-dependent vasodilatation and inotropy, lowers blood pressure, and promotes angiogenesis. The apelin system appears to protect against arrhythmias, inhibits thrombosis, and has broad anti-inflammatory and anti-fibrotic actions. It also promotes aqueous diuresis through direct and indirect (central) effects in the kidney. Thus, the apelin system offers therapeutic promise for a range of cardiovascular, kidney, and metabolic diseases. This review will discuss current cardiovascular disease targets of the apelin system and future clinical utility of apelin receptor agonism.
Topics: Humans; Apelin; Apelin Receptors; Cardiovascular Diseases; Cardiovascular System; Heart
PubMed: 37956047
DOI: 10.1093/cvr/cvad171 -
Frontiers in Endocrinology 2021Apelin, a (neuro)vasoactive peptide, plays a prominent role in controlling body fluid homeostasis and cardiovascular functions. Experimental data performed in rodents... (Review)
Review
Apelin, a (neuro)vasoactive peptide, plays a prominent role in controlling body fluid homeostasis and cardiovascular functions. Experimental data performed in rodents have shown that apelin has an aquaretic effect its central and renal actions. In the brain, apelin inhibits the phasic electrical activity of vasopressinergic neurons and the release of vasopressin from the posterior pituitary into the bloodstream and in the kidney, apelin regulates renal microcirculation and counteracts in the collecting duct, the antidiuretic effect of vasopressin occurring the vasopressin receptor type 2. In humans and rodents, if plasma osmolality is increased by hypertonic saline infusion/water deprivation or decreased by water loading, plasma vasopressin and apelin are conversely regulated to maintain body fluid homeostasis. In patients with the syndrome of inappropriate antidiuresis, in which vasopressin hypersecretion leads to hyponatremia, the balance between apelin and vasopressin is significantly altered. In order to re-establish the correct balance, a metabolically stable apelin-17 analog, LIT01-196, was developed, to overcome the problem of the very short half-life (in the minute range) of apelin In a rat experimental model of vasopressin-induced hyponatremia, subcutaneously (.) administered LIT01-196 blocks the antidiuretic effect of vasopressin and the vasopressin-induced increase in urinary osmolality, and induces a progressive improvement in hyponatremia, suggesting that apelin receptor activation constitutes an original approach for hyponatremia treatment.
Topics: Apelin; Apelin Receptors; Brain; Humans; Neurons; Vasopressins; Water-Electrolyte Balance
PubMed: 34880830
DOI: 10.3389/fendo.2021.735515 -
European Journal of Pharmacology Sep 2021Apelin is an endogenous ligand of G protein-coupled receptor APJ. Apelin/APJ system is widely expressed in abundant tissues, especially bone, joint and muscle tissue.... (Review)
Review
Apelin is an endogenous ligand of G protein-coupled receptor APJ. Apelin/APJ system is widely expressed in abundant tissues, especially bone, joint and muscle tissue. This review focus on the effects of apelin/APJ system on locomotor system. An increasing number of evidence suggests that apelin/APJ system plays a crucial role in many physiological and pathological processes of locomotor system. Physiologically, apelin/APJ system promotes bone formation, muscle metabolism and skeletal muscle production. Pathologically, apelin/APJ system exacerbates osteoarthritis pathogenesis, whereas it alleviates osteoporosis. Besides, the level of apelin expression is regulated by different training modes, including continuous aerobic exercise, high-intensity interval training and resistance exercises. More importantly, exercise-induced apelin may be a potent pharmacological agent for the treatment of diseases and the regulation of physiological processes. Considering the pleiotropic effects of apelin on locomotor system, apelin/APJ system may be an important therapeutic target for locomotor system diseases.
Topics: Animals; Apelin; Apelin Receptors; Disease Models, Animal; Humans; Molecular Targeted Therapy; Musculoskeletal Diseases; Signal Transduction
PubMed: 34174264
DOI: 10.1016/j.ejphar.2021.174286 -
Clinica Chimica Acta; International... Aug 2018Apelin, a regulatory peptide, is a ligand of the APJ receptor that belongs to the G protein-coupled receptor family. Apelin and APJ are widely distributed in the body... (Review)
Review
Apelin, a regulatory peptide, is a ligand of the APJ receptor that belongs to the G protein-coupled receptor family. Apelin and APJ are widely distributed in the body and play potential physiological roles in the cytoprotection of many internal organs. This review article summarizes information about the roles of the apelin/APJ system in neurological, metabolic, hypertension, respiratory, gastrointestinal, hepatic, kidney and cancerous diseases. It is suggested that apelin positively affects the treatment of non-cancerous diseases and may be considered as a therapeutic drug in many illnesses. However, in cancers, apelin appears as a tumour growth stimulator, and its suggested role is as a marker in the diagnosis of tumour cancers in tissues. In summary, apelin has certain therapeutic abilities and can be useful in the treatment of, e.g., insulin resistance, hypertension, etc., but it also can sometimes serve as a negative factor.
Topics: Animals; Apelin; Diagnosis; Disease; Humans; Neoplasms; Therapeutics
PubMed: 29750964
DOI: 10.1016/j.cca.2018.05.012 -
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 -
Neuropeptides Jun 2021Apelin is an endogenous ligand of G protein-coupled receptor APJ. In recent years, many studies have shown that the apelin/APJ system has neuroprotective properties,... (Review)
Review
Apelin is an endogenous ligand of G protein-coupled receptor APJ. In recent years, many studies have shown that the apelin/APJ system has neuroprotective properties, such as anti-inflammatory, anti-oxidative stress, anti-apoptosis, and regulating autophagy, blocking excitatory toxicity. Apelin/APJ system has been proven to play a role in various neurological diseases and may be a promising therapeutic target for nervous system diseases. In this paper, the neuroprotective properties of the apelin/APJ system and its role in neurologic disorders are reviewed. Further understanding of the pathophysiological effect and mechanism of the apelin/APJ system in the nervous system will help develop new therapeutic interventions for various neurological diseases.
Topics: Animals; Apelin; Apelin Receptors; Apoptosis; Autophagy; Brain Injuries, Traumatic; Epilepsy; Humans; Inflammation; Ischemic Stroke; Mental Disorders; Mice; Models, Neurological; Nervous System Diseases; Neurodegenerative Diseases; Neuroprotective Agents; Neurotoxins; Oxidative Stress; Pain Management; Peptide Fragments; Rats; Signal Transduction
PubMed: 33640616
DOI: 10.1016/j.npep.2021.102131 -
Journal of Cellular Physiology Aug 2019APJ is a G protein-coupled receptor and its endogenous ligand is apelin. Studies have shown that apelin/APJ system is widely distributed in the body, especially highly... (Review)
Review
APJ is a G protein-coupled receptor and its endogenous ligand is apelin. Studies have shown that apelin/APJ system is widely distributed in the body, especially highly expressed in the vascular endothelial cells (ECs). Numerous reports have demonstrated that apelin/APJ system plays an important role in the regulation of ECs function. Our lab has demonstrated that apelin-13 is able to promote adhesion of monocyte-human umbilical vein EC via 14-3-3, and reactive oxygen species-autophagy signaling pathways. In this review, we concentrate on the regulatory mechanism of apelin/APJ system in EC, including promotion of proliferation, migration, and angiogenesis. Moreover, we also analyze the role of apelin/APJ on endothelial dysfunction-related diseases including atherosclerosis, diabetes, hypertension, and myocardial infarction. Finally, we summarize the most commonly used agonists and antagonists of APJ. Therefore, apelin/APJ system is expected to be a therapeutic target for the treatment of endothelial dysfunction-related diseases.
Topics: Animals; Apelin; Apelin Receptors; Endothelial Cells; Humans; Ligands; Signal Transduction
PubMed: 30585633
DOI: 10.1002/jcp.27942