Apelin improves cardiac output in patients with pulmonary arterial hypertension

Brash, Lauren; Barnes, Gareth; Brewis, Melanie; Church, Colin; Gibbs, Simon; Howard, Luke; Johnson, Martin; McGlinchey, Neil; Simpson, Joanne; Stirrat, Colin; Thomson, Stephen; Watson, Geoffrey; Welsh, David; Wilkins, Martin R.; Newby, David E.; Peacock, Andrew J.

doi:10.1183/13993003.congress-2015.pa2107

Cited by 13 publications

(14 citation statements)

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“…In pulmonary arterial hypertension, an unmet medical need with few effective treatments, apelin represents a promising therapeutic avenue since it improved cardiac output and lowered pulmonary vascular resistance in PAH patients, consistent with previous studies in rodents …”

Section: Introduction—the Apelinergic Systemsupporting

confidence: 87%

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: 87%

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

et al. 2018

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“…A study showed that Apelin could reduce myocardial damage in the PH rat model induced by monocrotaline and improve their right ventricle function [ 22 ]. Clinical studies show that the serum levels of Apelin in patients with PH are reduced, and an exogenous supplementation of it improves the clinical symptoms of PH to a certain extent and increases the cardiac output of patients with PH [ 23 ]. Recently, a serum Apelin test was used as a very important way to diagnose the severity of PH [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Association of brain natriuretic peptide gene polymorphisms with chronic obstructive pulmonary disease complicated with pulmonary hypertension and its mechanism

et al. 2018

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Objective: To examine the association between brain natriuretic peptide (BNP) gene single nucleotide polymorphisms (SNPs) and chronic obstructive pulmonary disease (COPD) and COPD with pulmonary hypertension (PH) and to analyze its mechanism. Methods: The genotypes of BNP at the rs198389, rs6668352, and rs198388 loci in 339 patients with COPD (205 in the COPD/PH− group and 134 in the COPD/PH+ group) and 125 healthy subjects were detected by PCR/Sanger sequencing. The serum levels of BNP, fibrinogen (Fbg), and Apelin were measured in all subjects by ELISA. Results: The BNP rs198389 locus G allele, rs6668352 locus A allele, and 198388 locus T allele were high risk factors for COPD (P<0.001). Logistics regression analysis showed that BNP rs198389 locus G allele, rs6668352 locus A allele, and rs198388 locus T allele were high risk factors for PH in COPD patients (all P<0.001). The levels of the serum BNP and Fbg protein in the control group, COPD/PH− group, and COPD/PH+ group increased successively, and the expression levels of Apelin protein decreased successively (all P<0.001). The BNP and Fbg protein levels in the wild-type, heterozygote, and mutant homozygote in BNP rs198389, rs6668352, and rs198388 loci increased successively, and the serum Apelin protein levels decreased successively (all P<0.001). Conclusion: The polymorphisms of BNP at the rs198389, rs6668352, and rs198388 loci are associated with the occurrence of COPD and COPD with PH, and the occurrence may be related to the abnormal expression level of BNP, Fbg, and Apelin protein in the serum.

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“…Apelin is an endogenous ligand for the APJ receptor that is present on endothelial cells, vascular smooth muscle cells, and cardiomyocytes . It was previously reported from a small randomized trial in 20 patients with PAH that systemic infusion of apelin (10–100 nmol/min) resulted in increased cardiac output and stroke volume and in a reduction of PVR . In two other small trials with respectively 8 and 12 subjects, administration of apelin infusion was also demonstrated to have a positive effect on cardiac output, systemic blood pressure and peripheral vascular resistance in patients with chronic left‐sided heart failure .…”

Section: Treatmentmentioning

confidence: 99%

Right heart dysfunction and failure in heart failure with preserved ejection fraction: mechanisms and management. Position statement on behalf of the Heart Failure Association of the European Society of Cardiology

Gorter

Veldhuisen

Bauersachs

et al. 2017

European J of Heart Fail

269

223

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There is an unmet need for effective treatment strategies to reduce morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF). Until recently, attention in patients with HFpEF was almost exclusively focused on the left side. However, it is now increasingly recognized that right heart dysfunction is common and contributes importantly to poor prognosis in HFpEF. More insights into the development of right heart dysfunction in HFpEF may aid to our knowledge about this complex disease and may eventually lead to better treatments to improve outcomes in these patients. In this position paper from the Heart Failure Association of the European Society of Cardiology, the Committee on Heart Failure with Preserved Ejection Fraction reviews the prevalence, diagnosis, and pathophysiology of right heart dysfunction and failure in patients with HFpEF. Finally, potential treatment strategies, important knowledge gaps and future directions regarding the right side in HFpEF are discussed.

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Apelin improves cardiac output in patients with pulmonary arterial hypertension

Cited by 13 publications

References 0 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

Association of brain natriuretic peptide gene polymorphisms with chronic obstructive pulmonary disease complicated with pulmonary hypertension and its mechanism

Right heart dysfunction and failure in heart failure with preserved ejection fraction: mechanisms and management. Position statement on behalf of the Heart Failure Association of the European Society of Cardiology

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