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Symbol APLN contributors: mct/npt - updated : 16-04-2016
HGNC name apelin
HGNC id 16665
  • secretory signal sequence
  • apelin family
  • CATEGORY immunity/defense
    intracellular,nuclear envelope
    basic FUNCTION
  • neuropeptide expressed in the supraoptic and paraventricular nuclei acting on specific receptors located on vasopressinergic neurons
  • stimulates myosin light chain phosphorylation in vascular smooth muscle cells
  • endogenous ligands for the G protein-coupled receptor APJ (APLNR) (Medhurst 2003)
  • potent stimulators of cardiac contractility contributing to the pathophysiology of cardiac heart failure
  • stomach peptide with a potential physiological role in the gastrointestinal tract
  • angiogenic factor in retinal endothelial cells
  • acting as a novel adipocyte endocrine secretion and having a potential link with obesity-associated variations of insulin sensitivity status
  • promote tumor angiogenesis
  • produces direct cardioprotective actions involving the reperfusion injury salvage kinase pathway and the mitochondrial permeability transition pore (Simpkin 2007)
  • mitogenic for endothelial cells, and potent activator of tumour neoangiogenesis (Sorli 2007)
  • plays an important role in heart physiology and pathophysiology, inflammation, and angiogenesis (Principe 2008)
  • is a novel growth factor for embryonic stem cells-derived hematopoietic and endothelial cells
  • modulated the proliferation, migration, spreading, survival of Müller cells and the expressions of GFAP and VEGFA
  • beneficial adipokine with anti-insulin resistance properties
  • released from endothelial cells, regulates vascular tone and myocardial contractility in VSMC and cardiomyocytes
  • APLN/APLNR system functions as a critical mediator of cardiovascular homeostasis and is involved in the pathophysiology of cardiovascular diseases.
  • is a positive regulator of ACE2 in failing hearts
  • may play a profibrotic role in the development of proliferative diabetic retinopathy (PDR)
  • antioxidant properties of apelin in adipocytes
  • plays a prominent role in body fluid and cardiovascular homeostasis
  • APLN/APLNR axis is involved in hypoxia-induced proliferation of Endothelial progenitor cells (EPCs)
  • APLN and APLNR may play a role in human follicular development and the pathogenesis of polycystic ovary syndrome (PCOS)
  • is a novel myokine and may play a key role in regulating energy metabolism
  • spinal apelin&
  • 8209;APLNR system may drive neuropathic pain
    a component
  • APLN forms a heterodimer with OPRK1 and leads to increased PKC and decreased protein kinase A activity leading to a significant increase in cell proliferation
    small molecule
  • AGTRL1 receptor ligand
  • ACE2 hydrolyzes APLN with similar potency to AGT and, therefore, is responsible for the degradation of both peptides
  • its expression is strongly downregulated by BMP in an endothelial cell line as well as in lung endothelial microvascular cells
  • APLN, APLNR signaling is a potent regulator of endothelial MEF2C function in the developing cardiovascular system
  • induced the proliferation and migration of VSMCs as well as the upregulation of SPP1 via the upregulation of EGR1
  • endogenous ligand for the G-protein-coupled APLNR and plays an important role in regulating the cardiovascular system
  • is a second catalytic substrate for ACE2 and functions as an inotropic and cardioprotective peptide
  • is down-regulated by ATF4 via the pro-apoptotic MAPK14 pathway under endoplasmic reticulum (ER) stress
  • is a key regulator of cardiovascular function and is activated by two different endogenous peptide ligands, APLN and APELA, each with different isoforms diversified by length and amino acid sequence
  • orphan receptor GPR25 possesses two potential ligands APLN and APELA and its activation decreases intracellular cAMP levels in non-mammalian vertebrates, but also facilitates to unravel the physiological roles of GPR25 signaling in vertebrates
  • cell & other
    repressed by regulated in a tissue-dependent manner and according to the severity of insulin resistance (Dray 2010)
    Other regulated by insulin in adipocytes
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in cardiac heart failure and coronary heart disease
    constitutional     --over  
    during adipocyte differentiation stage
    constitutional     --over  
    in hepatic cirrhosis (Principe 2008)
    constitutional     --other  
    might be involved in the mechanism of establishment of overt diabetes mellitus as well as associated atherosclerotic complications (Erdem 2008)
    constitutional     --over  
    in aortic valve stenosis, of the apelin-APLNR signaling pathway (Peltonen 2009)
    constitutional     --low  
    in women with polycystic ovary syndrome
    constitutional     --over  
    of APLN or APLNR promoted the hypoxia-induced proliferation of the Endothelial progenitor cells (EPCs)
    Variant & Polymorphism
    Candidate gene
    Therapy target
    diabetemetabolic syndrom 
    autocrine signaling of apelin may serve as a novel therapeutic target for obesity and other metabolic disorders
    autocrine signaling of apelin may serve as a novel therapeutic target for obesity and other metabolic disorders
    blocking apelin signaling with anti-apelin antibodies will lead not only to inhibition of angiogenesis in adipose tissue but also to decreased adiposity
    apelin-APLNR signaling pathway, is a possible novel target for drug discovery in calcified aortic valve disease by suppressing chemotaxis, angiogenesis and osteoblast activity, all of which are well-documented phenomena in the disease process
    hepatic apelin system is a novel therapeutic target in liver disease