ELABELA Improves Cardio-Renal Outcome in Fatal Experimental Septic Shock

Coquerel, David; Chagnon, Frédéric; Sainsily, Xavier; Dumont, L; Murza, Alexandre; Côté, Jérôme; Dumaine, Robert; Sarret, Philippe; Marsault, Éric; Salvail, Dany; Auger‐Messier, Mannix; Lesur, Olivier

doi:10.1097/ccm.0000000000002639

Cited by 55 publications

(91 citation statements)

References 56 publications

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“…Indeed, infusion of apelin‐13 increases cardiac contractility while decreasing cardiac loading (positive inotropic effect), dilates blood vessels without compromising their permeability, and promotes blood vessel sprouting . Similar results were observed with ELA . While the apelinergic system is abundantly expressed in endothelial cells to regulate the properties of the vascular system, recent findings highlighting its significant expression in platelets suggest it might exert antithrombotic actions that require further study .…”

Section: Introduction—the Apelinergic Systemsupporting

confidence: 53%

“…In a sepsis model, the two ligands act differently on renal function while ELA does not show aquaretic effect and does not alter AVP bloodstream levels, contrarily to apelin . Interestingly, ELA also manifests a superior cardio‐renal protective effect and significantly improves the clinical score compared to apelin‐13 in this model …”

Section: Introduction—the Apelinergic Systemmentioning

confidence: 76%

“…Based on the above distribution and physiological effects, the apelinergic system emerges primarily as a potential target for the treatment of cardiovascular and metabolic disorders. Accordingly, the apelins and ELA showed beneficial effects in several animal models of chronic diseases such as heart failure, pulmonary arterial hypertension (PAH), obesity with insulin resistance, or acute conditions such as cardiac ischemia in mice and sepsis‐induced cardiac dysfunction in rat …”

Section: Introduction—the Apelinergic Systemmentioning

confidence: 99%

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Apelins, ELABELA, and their derivatives: Peptidic regulators of the cardiovascular system and beyond

et al. 2018

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The apelinergic system emerges as an important regulator of cardiovascular functions via its actions on the heart, vasculature, and kidney. It also possesses additional beneficial properties, via its actions on the pancreas and skeletal muscle, on type 2 diabetes. The apelinergic system distinguishes itself by the presence of two structurally distinct sets of endogenous ligands, the Apelins (–13, −17, and −36) and Elabela, which both activate the apelin (APJ) receptor. In the past decade, numerous peptidic ligands have been used to better understand the structure–activity relationship of apelin (and more recently Elabela), providing important tools to rationalize how ligand modifications impact receptor structure and dynamics as well as its downstream signaling. The recently disclosed structure of the apelin receptor in complex with an analogue of apelin‐17 provides an important tool in this quest. In this review, we first summarize the physiopharmacology of the apelinergic system, then, review existing knowledge on the various ligands of the apelin receptor with an emphasis on peptidic ligands, although small molecules are covered as well. Throughout this work, we tried to integrate existing knowledge of ligands’ pharmacological profiles with structure and signaling profile.

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Section: Introduction—the Apelinergic Systemsupporting

confidence: 53%

Section: Introduction—the Apelinergic Systemmentioning

confidence: 76%

Section: Introduction—the Apelinergic Systemmentioning

confidence: 99%

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Apelins, ELABELA, and their derivatives: Peptidic regulators of the cardiovascular system and beyond

et al. 2018

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“…Considering the known functions of ELA in protection against tissue injury, promotion of cell survival, and reduction of blood pressure [10,11,[27][28][29][30][31], it may be reasonable to speculate that the decrease of kidney ELA expression is not just a simple marker for kidney damage but may actually contribute to the DKD symptoms mentioned above. More studies are warranted to delineate the role of ELA in DKD or other kidney injuries.…”

Section: Discussionmentioning

confidence: 99%

Serum Elabela/Toddler Levels Are Associated with Albuminuria in Patients with Type 2 Diabetes

Zhang

Gong

et al. 2018

Cell Physiol Biochem

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Background/Aims: Elabela (ELA) or Toddler is a recently identified hormone that plays a crucial role in embryonic development through the activation of the apelin receptor (APJ). Our previous study indicated that ELA is highly expressed in adult kidney and the ELA receptor signaling pathway is functional in mammalian systems. Whereas nothing is yet known regarding ELA and diabetic kidney disease (DKD). Here, we evaluated the relationship between serum ELA levels and albuminuria in patients with type 2 diabetes (T2D). Methods: An observational study involving 80 patients divided into groups according to their baseline urinary albumin/creatinine ratio (ACR): Group 1 (ACR ≤ 29 mg/g), Group 2 (ACR = 30–299 mg/g), Group 3 (ACR ≥ 300 mg/g with normal serum creatinine), and Group 4 (ACR ≥ 300 mg/g with increased serum creatinine). The demographic, clinical, and biochemical variables including serum ELA were obtained or measured through disease history, physical examination, or laboratory evidence. Results: The results showed that the serum ELA levels decreased gradually with the deterioration of DKD from the stages of normal albuminuria, microalbuminuria, macroalbuminuria, to macroalbuminuria and elevated serum creatinine. In addition, ELA had a significantly negative correlation with ACR (r = -0.561, P < 0.001), retinopathy (r = -0.424, P < 0.001), serum creatinine (r = -0.269, P = 0.016), SBP (r = -0.249, P = 0.026), DBP (r = -0.261, P = 0.020) and a positive correlation with eGFR (r = 0.318, P = 0.004). Furthermore, stepwise multiple linear regression analysis showed that ACR, retinopathy, and LDL-C were considered the most relevant variables to ELA, and ELA, retinopathy, eGFR, and age were important predictors for ACR (t = -4.546, P = 0.000). Conclusions: To our knowledge, this is the first study to explore the clinical relationship between ELA levels and CKD. Decreased serum ELA levels might be a significant clinical predictor in patients with DKD or even as a promising agent for treating CKD patients.

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“…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%

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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ELABELA Improves Cardio-Renal Outcome in Fatal Experimental Septic Shock

Cited by 55 publications

References 56 publications

Apelins, ELABELA, and their derivatives: Peptidic regulators of the cardiovascular system and beyond

Apelins, ELABELA, and their derivatives: Peptidic regulators of the cardiovascular system and beyond

Serum Elabela/Toddler Levels Are Associated with Albuminuria in Patients with Type 2 Diabetes

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

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