Elabela, a newly discovered APJ ligand: Similarities and differences with Apelin

Zhang, Yixian; Wang, Yonggang; Lou, Yan; Luo, Manyu; Lu, Yen‐Shen; Li, Zhuo; Wang, Yangwei; Miao, Lining

doi:10.1016/j.peptides.2018.09.006

Cited by 48 publications

(60 citation statements)

References 154 publications

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“…3 Exogenous apela can interact with APJ receptors in mammalian tissues and cells to exert corresponding biological effects. [4][5][6][7][8][9][10] Previous basic experiments have also shown that apelin can improve cardiac function in mice with myocardial infarction by inhibiting myocardial cell apoptosis, promoting angiogenesis and inhibiting myocardial fibrosis. 11 Sustained apela gene therapy can improve blood pressure in high-salt diet hypertension rats.…”

Section: Introductionmentioning

confidence: 99%

Apela improves cardiac and renal function in mice with acute myocardial infarction

Pan

Hong

et al. 2020

J Cellular Molecular Medi

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Apela was recently identified as a new ligand of the apelin peptide jejunum (APJ) receptor. The purpose of this study was to investigate the role of apela in post‐myocardial infarction (post‐MI) recovery from cardiorenal damage. A murine MI model was established, and apela was then infused subcutaneously for two weeks. Echocardiographs were performed before and after infarction at the indicated times. Renal function was evaluated by serum and urine biochemistry. Immunohistochemistry of heart and kidney tissue was performed by in situ terminal deoxynucleotidyl transferase‐mediated dUPT nick end‐labelling reaction. Compared to the control group (MI/vehicle), the average value of the left ventricular ejection fraction in apela‐treated mice increased by 32% and 39% at 2‐ and 4‐week post‐MI, respectively. The mean levels of serum blood urea nitrogen，creatinine, N‐terminal pro‐brain natriuretic peptide and 24‐hour urine protein were significantly decreased at 4‐week post‐MI in apela‐treated mice relative to that of control animals. At the cellular level, we found that apela treatment significantly reduced myocardial fibrosis and cellular apoptosis in heart and kidney tissue. These data suggest that apela improves cardiac and renal function in mice with acute MI. The peptide may be potential therapeutic agent for heart failure.

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Section: Introductionmentioning

confidence: 99%

Apela improves cardiac and renal function in mice with acute myocardial infarction

Pan

Hong

et al. 2020

J Cellular Molecular Medi

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“…Some different effects of Apelin and Elabela over the cardiovascular system have been shown in studies. They contribute to the formation of heart and angiogenesis in the embryonic period, have inotropic effects, can cause vasodilatation in both systemic and pulmonary vascular systems, can reduce the development of cardiac hypertrophy and fibrosis, and may improve HF and myocardial infarction clinic (2,4,8,13,16) . Therefore, it is thought that this may be a treatment method because of all these positive and cardiovascular protective effects (8,17) .…”

Section: Discussionmentioning

confidence: 99%

“…These physiopathological processes, which initially increase ventricular performance, may result in decreased cardiac performance and HF symptoms occurred. Although there is no clear relationship between all these physiopathological processes and the apelinergic system, the Apelin seems to be increased for protection purposes especially after myocardial infarction remodeling phase and in HF, and to have positive effects by blocking the RAA system (2,4,8,13) . Recently, in a study conducted on mice, Elabela has been shown to protect the heart from cardiac dysfunction, hypertrophy and fibrosis development as a result of pressure over the heart (16) .…”

Section: Research Articlementioning

confidence: 99%

“…To the best of our knowledge, the association between natriuretic peptides and Apelin or Elabela is unknown. Both of these apelinergic system peptides have attenuating or slowing effects over myocardial hypertrophy and fibrotic processes (2) . We feel that due to these protective effects, Elabela might have a treatment potential in some cardiovascular diseases including HF (17) .…”

Section: Research Articlementioning

confidence: 99%

“…It has been reported that this system plays an important role in cardiovascular system modulation and has cardioprotective effects via Apelin's peptide and APJ receptor (2)(3)(4) . Elabela and Apelin antagonize the RAA system in patients with HF, reduce remodeling, increase myocardial vascularity, cause peripheral vasodilation, increase cardiac output, and are therefore considered to play a very important role in preventing cardiovascular disease and slowing disease progression in patients with HF (2,(5)(6)(7)(8)(9)(10)(11)(12) . To the best our knowledge, there is an increase in Apelin levels in patients with HFrEF (13) .…”

Section: Introductionmentioning

confidence: 99%

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Increased Serum Elabela Level Related to NT-proBNP in Patients with Heart Failure

Bulut¹,

Acele²,

Dönmez³

et al. 2020

ejcm

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Apelin levels have been shown to be increased in heart failure with reduced ejection fraction (HFrEF). However, the Elabela level in this patient group and its relationship with laboratory parameters are not clearly known. The aim of this study was to investigate the change in serum Elabela level in patients with HFrEF and its relationship with other clinical, laboratory and echocardiographic parameters. Materials and Methods: The study included 89 patients with HFrEF and 73 age-sex-matched healthy controls. Serum Elabela level was measured in addition to routine anamnesis, physical examination, laboratory and echocardiography examinations. Results: In patients with HFrEF; aspartate aminotransferase (AST), alanine aminotransferase (ALT), high-sensitivity C-reactive protein (hs-CRP), N-terminal pro B-type natriuretic peptide (NT-proBNP), and Elabela levels were significantly higher than those in healthy controls. Serum Elabela level was found to be positively correlated with blood urea nitrogen, AST, ALT, NT-proBNP, hs-CRP levels, left ventricular (LV) and left atrium (LA) diameters and volumes but negatively correlated with LV ejection fraction (LVEF). It was found that these parameters were only closely related to NT-proBNP, LVEF and LA end-diastolic diameter. Conclusion: The serum Elabela level in patients with HFrEF is significantly increased, and this is closely related to NT-proBNP, LA end-diastolic diameter and LVEF. Increased Elabela value in patients with HFrEF is closely related to NYHA class-III patients.

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Elabela, a Novel Peptide, Exerts Neuroprotective Effects Against Ischemic Stroke Through the APJ/miR-124-3p/CTDSP1/AKT Pathway

Zhang¹,

Li²,

Hou³

et al. 2023

Cell Mol Neurobiol

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Elabela (ELA), which is the second endogenous peptide ligand of the apelin receptor (APJ) to be discovered, has been widely studied for potential use as a therapeutic peptide. However, its role in ischemic stroke (IS), which is a leading cause of disability and death worldwide and has limited therapeutic options, is uncertain. The aim of the present study was to investigate the beneficial effects of ELA on neuron survival after ischemia and the underlying molecular mechanisms. Primary cortical neurons were isolated from the cerebral cortex of pregnant C57BL/6J mice. Flow cytometry and immunofluorescence showed that ELA inhibited oxygen–glucose deprivation (OGD) -induced apoptosis and axonal damage in vitro. Additionally, analysis of the Gene Expression Omnibus database revealed that the expression of microRNA-124-3p (miR-124-3p) was decreased in blood samples from patients with IS, while the expression of C-terminal domain small phosphatase 1 (CTDSP1) was increased. These results indicated that miR-124-3p and CTDSP1 were related to ischemic stroke, and there might be a negative regulatory relationship between them. Then, we found that ELA significantly elevated miR-124-3p expression, suppressed CTDSP1 expression, and increased p-AKT expression by binding to the APJ receptor under OGD in vitro. A dual-luciferase reporter assay confirmed that CTDSP1 was a direct target of miR-124-3p. Furthermore, adenovirus-mediated overexpression of CTDSP1 exacerbated neuronal apoptosis and axonal damage and suppressed AKT phosphorylation, while treatment with ELA or miR-124-3p mimics reversed these effects. In conclusion, these results indicated that ELA could alleviate neuronal apoptosis and axonal damage by upregulating miR-124-3p and activating the CTDSP1/AKT signaling pathway. This study, for the first time, verified the protective effect of ELA against neuronal injury after ischemia and revealed the underlying mechanisms. We demonstrated the potential for the use of ELA as a therapeutic agent in the treatment of ischemic stroke. Graphical Abstract

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Elabela, a newly discovered APJ ligand: Similarities and differences with Apelin

Cited by 48 publications

References 154 publications

Apela improves cardiac and renal function in mice with acute myocardial infarction

Apela improves cardiac and renal function in mice with acute myocardial infarction

Increased Serum Elabela Level Related to NT-proBNP in Patients with Heart Failure

Elabela, a Novel Peptide, Exerts Neuroprotective Effects Against Ischemic Stroke Through the APJ/miR-124-3p/CTDSP1/AKT Pathway

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