Apela Promotes Cardiomyocyte Differentiation from Transgenic Human Embryonic Stem Cell Lines

Wang, Zhi; Huang, Jin

doi:10.1007/s12010-019-03012-2

Cited by 8 publications

(8 citation statements)

References 49 publications

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“…1,2 Functional studies have also shown that apela and apelin can promote cardiomyocyte differentiation, induce angiogenesis and dilate aorta in vitro. [21][22][23][24] In vivo experiments have found that apelin and its structural homologs can alleviate myocardial ischaemia and reperfusion injury. 25,26 Sato et al showed that apela can prevent pressure overload heart failure caused by transverse aortic constriction in mice.…”

Section: Discussionmentioning

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: Discussionmentioning

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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“…Although the exact mechanism involved is still unknown, it is clear that ELA can enhance the cardiacrestricted transcription factors Tbx5 and GATA4 to promote the differentiation of hESCs into cardiomyocytes ( Fig. 1) [28]. The primary signaling pathways are summarized to give us deeper understanding of ELA-APJ axis (Fig.…”

Section: The Ela-apj Axis and Cardiorenal Dysfunctionmentioning

confidence: 99%

“…The Fmoc strategy, a special method of protein synthesis on solid phase, was employed to synthesize ELA and subsequently degraded ELA to identify the bioactive fragments [79]. ELA (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32) which possesses a highly similar structure to apelin-13, binds to APJ, activates the Gαi1 and β-arrestin-2 signaling pathways to lower blood pressure levels, and exerts positive inotropic effects [17]. ELA-11 (ELA22-32) inhibited I/R injuryinduced renal damage, including fibrosis, inflammation, and apoptosis, and preserved renal dysfunction in an AKI mouse model [18].…”

Section: The Ela-apj Axis and Cardiorenal Dysfunctionmentioning

confidence: 99%

“…Cell therapy is a promising therapeutic approach to restore cardiac function. ELA was verified as a growth factor that promotes cardiomyocyte differentiation from transgenic hESCs to remedy the loss of cardiomyocytes in HF [28]. In the light of the limitation in translating lead compounds to clinical applications, investigators have identified and developed biased and nonbiased agonists toward APJ receptor and other GPCR signaling [32].…”

Section: The Ela-apj Axis and Cardiorenal Dysfunctionmentioning

confidence: 99%

“…Notably, ELA and apelin share the same receptor and exert similar biological effects. Therefore, a family consisting of ELA, apelin, and APJ named the apelinergic system plays cardiotonic, diuretic, depressor, and cardiorenal protective roles (Table 1) [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. The underlying mechanisms of the ELA-APJ axis remain largely unclear despite their clinical importance.…”

Section: Introductionmentioning

confidence: 99%

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The Elabela-APJ axis: a promising therapeutic target for heart failure

Song

Martin

et al. 2020

Heart Fail Rev

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Heart failure (HF) is a growing epidemic with high morbidity and mortality at an international scale. The apelin-APJ receptor pathway has been implicated in HF, making it a promising therapeutic target. APJ has been shown to be activated by a novel endogenous peptide ligand known as Elabela (ELA, also called Toddler or Apela), with a critical role in cardiac development and function. Activation of the ELA-APJ receptor axis exerts a wide range of physiological effects, including depressor response, positive inotropic action, diuresis, anti-inflammatory, anti-fibrotic, and anti-remodeling, leading to its cardiovascular protection. The ELA-APJ axis is essential for diverse biological processes and has been shown to regulate fluid homeostasis, myocardial contractility, vasodilation, angiogenesis, cellular differentiation, apoptosis, oxidative stress, cardiorenal fibrosis, and dysfunction. The beneficial effects of the ELA-APJ receptor system are well-established by treating hypertension, myocardial infarction, and HF. Additionally, administration of ELA protects human embryonic stem cells against apoptosis and stress-induced cell death and promotes survival and self-renewal in an APJ-independent manner (X receptor) via the phosphatidylinositol 3-kinase/Akt pathway, which may provide a new therapeutic approach for HF. Thus, targeting the ELA-APJ axis has emerged as a pre-warning biomarker and a novel therapeutic approach against progression of HF. An increased understanding of cardiovascular actions of ELA will help to develop effective interventions. This article gives an overview of the characteristics of the ELA-apelin-APJ axis and summarizes the current knowledge on its cardioprotective roles, potential mechanisms, and prospective application for acute and chronic HF.

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