Recombinant Fc-Elabela fusion protein has extended plasma half-life andmitigates post-infarct heart dysfunction in rats

Xi, Yue; Yu, Dihua; Yang, Rongze; Zhao, Qingbin; Wang, Junhong; Zhang, Hong; Qian, Kun; Shi, Zhengrong; Wang, Weimin; Brown, Robert A.; Li, Yongxia; Tian, Zhenjun; Gong, Da-Wei

doi:10.1016/j.ijcard.2019.04.089

Cited by 24 publications

(26 citation statements)

References 47 publications

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“…1) [25,27,59]. This in vitro work demonstrated that apoptosis after MI was suppressed by administration of ELA in the experimental group compared with controls [25]. Stem cell exhaustion has been recognized as a common factor in age-related diseases such as HF.…”

Section: The Ela-apj Axis and Blood Pressure Regulationmentioning

confidence: 72%

“…Moreover, ELA is also considered to be a factor affecting cell growth and cell cycle progression, meaning that it may affect cardiac fibroblasts (CFs) and ECs in impaired hearts ( Fig. 1) [25,27,59]. This in vitro work demonstrated that apoptosis after MI was suppressed by administration of ELA in the experimental group compared with controls [25].…”

Section: The Ela-apj Axis and Blood Pressure Regulationmentioning

confidence: 72%

“…Adverse cardiac remodeling is the primary characteristic of myocardial fibrosis and dysfunction. In a rat model of myocardial infarction (MI), pretreatment with ELA significantly reduced the severity of cardiac fibrosis and improved hemodynamic parameters obtained from the invasive catheter examination, such as LV systolic pressure, LV end-diastolic pressure, and maximal positive and negative first derivative of LV pressure (Table 1) [25]. Administration of ELA further limited the area of cardiac fibrosis in a murine MI model with downregulated levels of profibrotic genes, including transforming growth factor-β (TGFβ), latent TGFβ-binding protein 2, periostin, and collagen 8a [14], suggesting that ELA blunts the process of myocardial fibrosis and the loss of cardiomyocytes secondary to MI, thereby preserving cardiac function.…”

Section: The Ela-apj Axis and Blood Pressure Regulationmentioning

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%

“…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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Section: The Ela-apj Axis and Blood Pressure Regulationmentioning

confidence: 72%

Section: The Ela-apj Axis and Blood Pressure Regulationmentioning

confidence: 72%

Section: The Ela-apj Axis and Blood Pressure Regulationmentioning

confidence: 99%

Section: The Ela-apj Axis and Cardiorenal Dysfunctionmentioning

confidence: 99%

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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Apelin Receptor Signaling During Mesoderm Development

Sağraç

Şişli

Doğan

2020

Cell Biology and Translational Medicine, Volume 10

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Human TFF2-Fc fusion protein alleviates DSS-induced ulcerative colitis in C57BL/6 mice by promoting intestinal epithelial cells repair and inhibiting macrophage inflammation

et al. 2023

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The clinical drugs for ulcerative colitis mainly affect the inflammatory symposiums with limited outcomes and various side effects. Repairing the damaged intestinal mucosa is a promising and alternative strategy to treat ulcerative colitis. Trefoil factor family 2 (TFF2) could repair the intestinal mucosa, however, it has a short half-life in vivo. To improve the stability of TFF2, we have prepared a new fusion protein TFF2-Fc with much stability, investigated the therapeutic effect of TFF2-Fc on ulcerative colitis, and further illustrated the related mechanisms. We found that intrarectally administered TFF2-Fc alleviated the weight loss, the colon shortening, the disease activity index, the intestinal tissue injury, and the lymphocyte infiltration in dextran sulfate sodium (DSS)-induced colitis mice. In vitro, TFF2-Fc inhibited Caco2 cells injury and apoptosis, promoted cellular migration, and increased the expression of Occludin and ZO-1 by activating P-ERK in the presence of H 2 O 2 or inflammatory conditioned medium (LPS-RAW264.7/CM). Moreover, TFF2-Fc could reduce lipopolysaccharide (LPS)-induced production of inflammation cytokines and reactive oxygen species in RAW264.7 cells, and also inhibits the polarization of RAW264.7 cells to M1 phenotype by reducing glucose consumption and lactate production. Taken together, in this work, we have prepared a novel fusion protein TFF2-Fc, which could alleviate ulcerative colitis in vivo via promoting intestinal epithelial cells repair and inhibiting macrophage inflammation, and TFF2-Fc might serve as a promising ulcerative colitis therapeutic agent.

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Recombinant Fc-Elabela fusion protein has extended plasma half-life andmitigates post-infarct heart dysfunction in rats

Cited by 24 publications

References 47 publications

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

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

Apelin Receptor Signaling During Mesoderm Development

Human TFF2-Fc fusion protein alleviates DSS-induced ulcerative colitis in C57BL/6 mice by promoting intestinal epithelial cells repair and inhibiting macrophage inflammation

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