Apelin Compared With Dobutamine Exerts Cardioprotection and Extends Survival in a Rat Model of Endotoxin-Induced Myocardial Dysfunction*

Chagnon, Frédéric; Coquerel, David; Salvail, Dany; Marsault, Éric; Dumaine, Robert; Auger‐Messier, Mannix; Sarret, Philippe; Lesur, Olivier

doi:10.1097/ccm.0000000000002097

Cited by 33 publications

(32 citation statements)

References 44 publications

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“…In physiological conditions, both ligands exert powerful cardiac and vasoactive actions . 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 .…”

Section: Introduction—the Apelinergic Systemsupporting

confidence: 58%

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: 58%

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

et al. 2018

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“…In experimental and clinical conditions, endotoxinmediated myocardial injury has been demonstrated to be related to increased cytokines 3,9,22 . The major cytokines that induce cardiac damage during endotoxemia are shown to include TNF-α and IL-6 10,11 .…”

Section: ■ Discussionmentioning

confidence: 99%

“…The heart is among the most affected organs by the systemic inflammatory response 7 . Cytokines have been suggested to be responsible for endotoxinmediated myocardial injury 8,9 . Increased myocardial and serum levels of TNF-α and IL-6 during Lps-mediated systemic inflammatory responses have shown to be associated with both cellular and functional cardiac deterioration 10,11 .…”

Section: ■ Introductionmentioning

confidence: 99%

TNF-alpha inhibitor adalimumab attenuates endotoxin induced cardiac damage in rats

et al. 2020

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Design of the study, acquisition and analysis of data, final approval. ORIGINAL ARTICLE Experimental SurgeryActa Cir Bras. 2020;35(2):e202000202 AbstractPurpose: To investigate the effects of adalimumab pretreatment on the lipopolysaccharide-mediated myocardial injury.Methods: Twenty-eight Wistar rats were randomized into four groups (n=7). Control (C) group animals were injected once a day with intraperitoneal (i.p) 0.9 % saline for two days. In the Adalimumab (Ada) group, adalimumab was injected at a dose of 10 mg/kg/ day (i.p) for two days. Lipopolysaccharide (Lps) group rats were injected with a dose of 5 mg/kg (i.p) lipopolysaccharide. Lipopolysaccharide + Adalimumab (Lps+Ada) group rats received adalimumab before the administration of lipopolysaccharide. The animals were sacrificed 24 h after the last injection and blood samples were obtained for determination of biochemical cardiac injury markers and circulating levels of TNF-α and interleukin-6 (IL-6). Hearts were harvested for histological examination.Results: Endotoxin exposure resulted in significant increases in serum cardiac injury markers, serum cytokines and histological myocardial injury scores in the Lps group. The levels of circulating cytokines, cardiac injury markers and histological injury scores for myocardial necrosis, perivascular cell infiltration, and inflammation were significantly reduced in Lps+Ada as compared to Lps group (p<0.05). Conclusions:Adalimumab pretreatment reduces endotoxin-induced myocardial damage in rats. This beneficial effect is thought to be related to the reduction of cytokine release.

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“…Apelin-13, the most potent isoform of apelin, participates in the development of HF [19,41,42]. Furthermore, apelin-13 optimizes the cardiac workload and reduces vascular resistance to improve the cardiac index [43]. ELA, as a second endogenous ligand of APJ, has a similar inotropic effect.…”

Section: The Ela-apj Axis and Cardiac Contractilitymentioning

confidence: 99%

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

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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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Apelin Compared With Dobutamine Exerts Cardioprotection and Extends Survival in a Rat Model of Endotoxin-Induced Myocardial Dysfunction*

Abstract: In this inflammatory cardiovascular dysfunction, apelin-13 infusion delivers distinct and optimized hemodynamic support (including positive fluid balance), along with cardioprotective effects, modulation of circulatory inflammation and extended survival.

Cited by 33 publications

References 44 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

TNF-alpha inhibitor adalimumab attenuates endotoxin induced cardiac damage in rats

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

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