Apelin/APJ system: an emerging therapeutic target for respiratory diseases

Yan, Jialong; Wang, Aiping; Cao, Jun; Chen, Linxi

doi:10.1007/s00018-020-03461-7

Cited by 72 publications

(48 citation statements)

References 102 publications

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“…Apelin-13 has been reported to acutely enhance in the serum of patients with earlystage PE. Accordingly, apelin expression in lung tissue is up-regulated in a dog model of acute PE within the first hours and declined within 24 h, whereas intravenous administration of apelin reduces mean pulmonary arterial pressure and vascular resistance [18]. On the other hand, Ang-II elevation may cause the down-regulation of apelin and its receptor in the late stages of pathological status including hypoxia, which is a major manifestation of PE.…”

Section: Apelin and Covid-19mentioning

confidence: 95%

“…Apelin protects against ALI and ARDS through suppression of NF-κBand NLRP3 inflammasome-mediated inflammatory responses and secretion of IL-1β and IL-18 from cells. Apelin also down-regulates mitochondrial ROS-triggered oxidative damage and mitochondria apoptosis [18]. Studies of animal models of ARDS have shown that post-injury activation of apelin-APJ system alleviates pulmonary inflammation and lung injury responses, and improves the oxygenation and lung edema by activating Akt-eNOS signal transduction and inhibiting the pro-inflammatory tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and oxidative stress.…”

Section: Apelin and Covid-19mentioning

confidence: 99%

“…Deletion of apelin in the mice have been shown to induce the Ang-IImediated pro-fibrotic processes, e.g. transforming growth-factor beta (TGF-β) and matrix metalloproteinase (MMPs) signaling, in the heart and lung, while exogenous apelin attenuated the TGF-β expression and further Ang-II-stimulated cardiac remodeling and pulmonary fibrosis [18]. ALI/ARDS is certainly associated with pulmonary endothelial injury and inflammatory/oxidative/procoagulant responses.…”

Section: Apelin and Covid-19mentioning

confidence: 99%

“…In addition to the therapeutic effects, apelin can potentially act as a predictor in the development of coagulopathies and cardiovascular disorders, including pulmonary embolism (PE) [18]. Apelin-13 has been reported to acutely enhance in the serum of patients with earlystage PE.…”

Section: Apelin and Covid-19mentioning

confidence: 99%

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Apelin-potential therapy for COVID-19?

Saravi

Beer

2020

Journal of Molecular and Cellular Cardiology

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We believe that, in parallel to the attempts for direct blockade of the SARS-CoV-2 penetration into host cell and repurposing drugs, finding new therapeutic strategies for patients with lung injury or cardiovascular complications/coagulopathies associated with COVID-19 should be paid particular attention. Apelin or its receptor agonists are of great potential treatment for COVID-19 through suppressing angiotensin-converting enzyme (ACE) and angiotensin II (Ang-II) production, as well as, down-regulating angiotensin receptor 1 (AT1R) and ACE2 up-regulation. These drugs have potential to improve acute lung injury and cardiovascular/coagulopathy complications in COVID-19 which are associated with elevated Ang-II/Ang(1-7) ratio.

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Section: Apelin and Covid-19mentioning

confidence: 95%

Section: Apelin and Covid-19mentioning

confidence: 99%

Section: Apelin and Covid-19mentioning

confidence: 99%

Section: Apelin and Covid-19mentioning

confidence: 99%

See 2 more Smart Citations

Apelin-potential therapy for COVID-19?

Saravi

Beer

2020

Journal of Molecular and Cellular Cardiology

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“…The physiological consequences of ACE2 mediated inhibition of kinins and apelin cannot be underestimated. Whereas kinins are known for their inflammatory actions, apelin is thought to exert vasodilatory and anti-inflammatory actions such as endothelial nitric oxide synthase (eNOS) dependent vasodilatation, NF-Kβ inhibition and amelioration of mitochondrial dysfunction in endothelial and vascular smooth muscle cells (Andersen et al, 2011;Yan et al, 2020). Apelin, in cross-talk between its receptor APJ and the angiotensin-AT 1 receptor, suppresses AT 1 signalling and upregulates ACE2.…”

Section: Ace2 and Its Interplay With Other Peptides-apelin And Bradykmentioning

confidence: 99%

Should ACE2 be given a chance in COVID-19 therapeutics: A semi-systematic review of strategies enhancing ACE2

Kaur

Acharya

Mondal

et al. 2020

European Journal of Pharmacology

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The severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) has resulted in almost 28 million cases of COVID-19 (Corona virus disease-2019) and more than 900000 deaths worldwide since December 2019. In the absence of effective antiviral therapy and vaccine, treatment of COVID-19 is largely symptomatic. By making use of its spike (S) protein, the virus binds to its primary human cell receptor, angiotensin converting enzyme 2 (ACE2) which is present in the pulmonary epithelial cells as well as other organs. SARS-CoV-2 may cause a downregulation of ACE2. ACE2 plays a protective role in the pulmonary system through its Mas-receptor and alamandine-MrgD-TGR7 pathways. Loss of this protective effect could be a major component of COVID-19 pathogenesis. An attractive strategy in SARS-CoV-2 therapeutics would be to augment ACE2 either directly by supplementation or indirectly through drugs which increase its levels or stimulate its downstream players. In this semi-systematic review, we have analysed the pathophysiological interplay between ACE and ACE2 in the cardiopulmonary system, the modulation of these two proteins by SARS-CoV-2, and potential therapeutic avenues targeting ACE-Ang II and ACE2-Ang (1–7) axes, that can be utilized against COVID-19 disease progression.

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ELABELA/APJ Axis Prevents Diabetic Glomerular Endothelial Injury by Regulating AMPK/NLRP3 Pathway

Wang

Lin

et al. 2023

Inflammation

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ELABELA (ELA), a recently discovered peptide, is highly expressed in adult kidneys and the endothelium system. It has been identified as a novel endogenous ligand for the apelin receptor (APJ). This study aims to investigate the role of ELA in diabetic glomerular endothelial pyroptosis and its underlying mechanism. Initially, a significant decrease in ELA mRNA levels was observed in the renal cortex of db/db mice and high glucose–treated glomerular endothelial cells (GECs). It was also found that ELA deficiency in ELA+/− mice significantly accelerated diabetic glomerular injury, as shown by exacerbated glomerular morphological damage, increased serum creatine and blood urea nitrogen, and elevated 24-h urinary albumin excretion. In addition, in vivo overexpression of ELA prevented diabetic glomerular injury, reduced von Willebrand factor expression, restored endothelial marker CD31 expression, and attenuated the production of adhesive molecules such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Furthermore, in vitro studies confirmed that treatment with ELA inhibited GEC injury by regulating the NOD-like receptor protein 3 (NLRP3) inflammasome, as indicated by blocking NLRP3 inflammasome formation, decreasing cleaved Caspase-1 production, and inhibiting interleukin-1β and interleukin-18 production. Moreover, in vitro experiments demonstrated that the protective effects of ELA in GECs during hyperglycemia were diminished by inhibiting adenosine monophosphate–activated protein kinase (AMPK) using Compound C or by APJ deficiency. Taken together, this study provides the first evidence that ELA treatment could prevent diabetic glomerular endothelial injury, which is partly mediated by the regulation of the AMPK/NLRP3 signaling pathway. Therefore, pharmacologically targeting ELA may serve as a novel therapeutic strategy for diabetic kidney disease.

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Apelin/APJ system: an emerging therapeutic target for respiratory diseases

Cited by 72 publications

References 102 publications

Apelin-potential therapy for COVID-19?

Apelin-potential therapy for COVID-19?

Should ACE2 be given a chance in COVID-19 therapeutics: A semi-systematic review of strategies enhancing ACE2

ELABELA/APJ Axis Prevents Diabetic Glomerular Endothelial Injury by Regulating AMPK/NLRP3 Pathway

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