Apelin and Elabela/Toddler; double ligands for APJ/Apelin receptor in heart development, physiology, and pathology

Kuba, Keiji; Sato, Takeya; Imai, Yumiko; Yamaguchi, Tomokazu

doi:10.1016/j.peptides.2018.04.011

Cited by 71 publications

(61 citation statements)

References 114 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Apelin is another substrate of ACE2 and an endogenous peptide ligand to the G protein-coupled receptor, the APJ [75]. Apelin is expressed predominantly in the endothelium and acts locally via endocrine signaling to activate the APJ, which is expressed on the surface of myocardial cells and endothelial cells [18,72].…”

Section: The Physiology Of the Renin-angiotensin System And Ace2mentioning

confidence: 99%

“…In addition, the molecular interaction between AT1R and APJ suppresses the activity of AT1R [24]. The apelin/APJ axis reduces vascular tone, decreases blood pressure, regulates fluid homeostasis, improves cardiac contractility [75], and protects against heart [124] and lung injury [35]. In both oleic acid-and LPS-induced ARDS models, treatment with apelin-13 after injury attenuated the lung injury and improved oxygenation [35].…”

Section: The Physiology Of the Renin-angiotensin System And Ace2mentioning

confidence: 99%

See 1 more Smart Citation

Inflammation Triggered by SARS-CoV-2 and ACE2 Augment Drives Multiple Organ Failure of Severe COVID-19: Molecular Mechanisms and Implications

et al. 2020

View full text Add to dashboard Cite

The widespread occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a pandemic of coronavirus disease 2019 (COVID-19). The S spike protein of SARS-CoV-2 binds with angiotensin-converting enzyme 2 (ACE2) as a functional “receptor” and then enters into host cells to replicate and damage host cells and organs. ACE2 plays a pivotal role in the inflammation, and its downregulation may aggravate COVID-19 via the renin-angiotensin system, including by promoting pathological changes in lung injury and involving inflammatory responses. Severe patients of COVID-19 often develop acute respiratory distress syndrome and multiple organ dysfunction/failure with high mortality that may be closely related to the hyper-proinflammatory status called the “cytokine storm.” Massive cytokines including interleukin-6, nuclear factor kappa B (NFκB), and tumor necrosis factor alpha (TNFα) released from SARS-CoV-2-infected macrophages and monocytes lead inflammation-derived injurious cascades causing multi-organ injury/failure. This review summarizes the current evidence and understanding of the underlying mechanisms of SARS-CoV-2, ACE2 and inflammation co-mediated multi-organ injury or failure in COVID-19 patients.

show abstract

Section: The Physiology Of the Renin-angiotensin System And Ace2mentioning

confidence: 99%

Section: The Physiology Of the Renin-angiotensin System And Ace2mentioning

confidence: 99%

Inflammation Triggered by SARS-CoV-2 and ACE2 Augment Drives Multiple Organ Failure of Severe COVID-19: Molecular Mechanisms and Implications

et al. 2020

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

“…It is unclear whether all capillary ECs are equally important for hematopoiesis and HSC maintenance. Apelin, encoded by gene Apln, is a secreted peptide whose function is reported to be redundant with Elabela/Apela (Helker et al, 2015;Ho et al, 2017;Kim, 2014;Kuba et al, 2019). Apelin is primarily secreted from a subset of capillary ECs, namely, Apln + ECs, which can be genetically targeted by Apln-CreER knockin mice (Chen et al, 2016;Liu et al, 2015;Tian et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Apelin+ Endothelial Niche Cells Control Hematopoiesis and Mediate Vascular Regeneration after Myeloablative Injury

et al. 2019

View full text Add to dashboard Cite

show abstract

Apelin and Elabela/Toddler; double ligands for APJ/Apelin receptor in heart development, physiology, and pathology

Cited by 71 publications

References 114 publications

Inflammation Triggered by SARS-CoV-2 and ACE2 Augment Drives Multiple Organ Failure of Severe COVID-19: Molecular Mechanisms and Implications

Inflammation Triggered by SARS-CoV-2 and ACE2 Augment Drives Multiple Organ Failure of Severe COVID-19: Molecular Mechanisms and Implications

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

Apelin+ Endothelial Niche Cells Control Hematopoiesis and Mediate Vascular Regeneration after Myeloablative Injury

Contact Info

Product

Resources

About