ELABELA: a novel hormone in cardiac development acting as a new endogenous ligand for the APJ receptor

Xie, Feng; Lv, Deguan; Chen, Linxi

doi:10.1093/abbs/gmu032

Cited by 28 publications

(27 citation statements)

References 35 publications

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“…Although many detailed studies have highlighted the mechanisms of ERS in cardiovascular diseases, they have yielded conflicting results and additional studies should be conducted to elucidate these mechanisms. Other factors associated with ERS have also been searched, such as the apelin/APJ system [181,182] , in which both apelin-13 and ERS can regulate cardiomyocyte proliferation, migration and adhesion [183,184] . ERS induced ATF4 expression, regulating apelin-13 transcription via a p38 AMPK-dependent pathway.…”

Section: Endoplasmic Reticulum Stress Is Involved In the Development mentioning

confidence: 99%

Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases

2016

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Endoplasmic reticulum is a principal organelle responsible for folding, post-translational modifications and transport of secretory, luminal and membrane proteins, thus palys an important rale in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) is a condition that is accelerated by accumulation of unfolded/misfolded proteins after endoplasmic reticulum environment disturbance, triggered by a variety of physiological and pathological factors, such as nutrient deprivation, altered glycosylation, calcium depletion, oxidative stress, DNA damage and energy disturbance, etc. ERS may initiate the unfolded protein response (UPR) to restore cellular homeostasis or lead to apoptosis. Numerous studies have clarified the link between ERS and cardiovascular diseases. This review focuses on ERS-associated molecular mechanisms that participate in physiological and pathophysiological processes of heart and blood vessels. In addition, a number of drugs that regulate ERS was introduced, which may be used to treat cardiovascular diseases. This review may open new avenues for studying the pathogenesis of cardiovascular diseases and discovering novel drugs targeting ERS.

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Section: Endoplasmic Reticulum Stress Is Involved In the Development mentioning

confidence: 99%

Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases

2016

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“…Apelin is the endogenous ligand for APJ ( putative receptor protein related to the angiotensin receptor AT1) and plays a crucial role in the cardiovascular system [1]. Several apelin peptides, such as apelin-77, apelin-36, apelin-17, apelin-13, and apelin-12, have been shown to be present in vivo, all of which have different effects on the APJ receptor due to their different sizes [2].…”

Section: Introductionmentioning

confidence: 99%

Apelin-13 promotes cardiomyocyte hypertrophy via PI3K-Akt-ERK1/2-p70S6K and PI3K-induced autophagy

Xie

Liu

Feng

et al. 2015

ABBS

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Apelin is highly expressed in rat left ventricular hypertrophy Sprague Dawley rat models, and it plays a crucial role in the cardiovascular system. The aim this study was to clarify whether apelin-13 promotes hypertrophy in H9c2 rat cardiomyocytes and to investigate its underlying mechanism. The cardiomyocyte hypertrophy was observed by measuring the diameter, volume, and protein content of H9c2 cells. The activation of autophagy was evaluated by observing the morphology of autophagosomes by transmission electron microscopy, observing the subcellular localization of LC3 by light microscopy, and detecting the membrane-associated form of LC3 by western blot analysis. The phosphatidylinositol 3-kinase (PI3K) signaling pathway was identified and the proteins expression was detected using western blot analysis. The results revealed that apelin-13 increased the diameter, volume, and protein content of H9c2 cells and promoted the phosphorylation of PI3K, Akt, ERK1/2, and p70S6K. Apelin-13 activated the PI3K-Akt-ERK1/2-p70S6K pathway. PI3K inhibitor LY294002, Akt inhibitor 1701-1, ERK1/2 inhibitor PD98059 attenuated the increase of the cell diameter, volume, protein content induced by apelin-13. Apelin-13 increased the autophagosomes and up-regulated the expressions of beclin 1 and LC3-II/I both transiently and stably. The autophagy inhibitor 3MA ameliorated the increase of cell diameter, volume, and protein content that were induced by apelin-13. These results suggested that apelin-13 promotes H9c2 rat cardiomyocyte hypertrophy via PI3K-Akt-ERK1/2-p70S6K and PI3K-induced autophagy.

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“…Taken together, these data indicate that the apelin/APJ system regulates cardiac development via a G13-HDAC-MEF2 cascade. In zebrafish a role in cardiac development has also been attributed to ELABELA, the newly discovered hormone acting as a second ligand of APJ receptors [19,20]. Since apelin induces endothelial nitric oxide synthase (eNOS) phosphorylation in endothelial cells and nitric oxide (NO) participates to the process of angiogenesis [57,58], the role of apelin in vessel formation is expected to be mediated by NO.…”

Section: Molecular Mechanismsmentioning

confidence: 99%

“…While apelin-deficient mice are viable, fertile and show normal development, APJ-deficient mice display cardiovascular development defects, suggesting the possibility of undiscovered APJ ligands or ligand-independent effects of APJ [18]. An example of such APJ ligand is the ELABELA hormone, which is involved in heart development [19,20] while a ligand-independent effect might consist in the initiation of cardiac hypertrophy in response to stretch [21]. …”

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Effects of apelin on the cardiovascular system

et al. 2015

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Apelin is an endogenous peptide acting on the APJ receptor. It consists of several isoforms characterised by different numbers of aminoacids. The number of aminoacids in the active isoforms range from 36 to 12. Apelin-13 and, to a lesser extent, apelin-36 are considered the most active isoforms with the greatest activity on the cardiovascular homeostasis. The effects normally exerted by the basal level of endogenous apelin, can be enhanced not only by its up-regulation, but may also by its exogenous administration. The present review considers the effects of apelin on various aspects of the cardiovascular function, such as cardiac development, vasomotor tone, angiogenesis, myocardial inotropy in healthy and failing hearts as well as the prevention of ischemia-reperfusion injury, cardiac fibrosis and remodeling. Also the biphasic changes of apelin level during the evolution of heart failure are considered. Although the positive inotropic effect exerted by apelin in normal and failing hearts would suggest the use of this peptide in the treatment of heart failure, the limited duration and extent of its effect do not support this possibility, unless a long lasting (6 hours) infusion is performed to overcome the limit of its short life. However, although the data on the characteristics of the inotropic activity do not provide a strong support for the treatment of active heart failure, apelin may be used in the prevention of heart failure because of its activity in limiting the consequences of myocardial ischemia such as infarct size and cardiac remodeling. KeywordsApelin/APJ system, heart failure, ischemia-reperfusion injury, contractility, cardiac protection, Reninangiotensin system 2 The apelin/APJ system Apelin In 1998 Tatemoto et al. discovered the endogenous peptide capable of binding the G protein-coupled receptor (GPCR) APJ [1,2], which at that time was considered an orphan receptor becaue its ligand was unknown. The just discovered ligand was called, apelin e.g APj Endogenous LIgaNd. Apelin is expressed in hearts, lungs, kidneys, liver, adipose tissue, gastrointestinal tract, brain, adrenal glands, endothelium, and human plasma. The gene of apelin is located on chromosome X [3] and encodes a 77 aminoacid sequence called pre-pro-apelin [4]. Upon cleavage by a family of endopeptidases, pre-pro-apelin generates several C-terminal fragments of various size, which are classified on the basis of the number of aminoacids. The active isoforms range from 36 to 12 aminoacids. As fragments shorter than 12 aminoacids are biologically inactive, it appears evident that the Cterminal 12 aminoacids are essential for receptor binding, whereas the N-terminal sequence modulates the interaction with the receptor [5]. At present it is recognized that, although different isoforms display similar functions, active isoforms differ in tissue distribution, potency and receptor binding affinity [6]. Apelin-13 and, to a lesser extent, apelin-36 have been considered the most active isoforms with the greatest activity on the cardi...

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ELABELA: a novel hormone in cardiac development acting as a new endogenous ligand for the APJ receptor

Cited by 28 publications

References 35 publications

Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases

Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases

Apelin-13 promotes cardiomyocyte hypertrophy via PI3K-Akt-ERK1/2-p70S6K and PI3K-induced autophagy

Effects of apelin on the cardiovascular system

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