Plasma concentrations of the novel peptide apelin are decreased in patients with chronic heart failure

Abstract

Background: Apelin, the novel endogenous ligand for the G-protein-coupled receptor APJ, has shown positive inotropic, vasodilatory and diuretic properties in animal studies. Differential expression and synthesis of apelin and APJ receptors have been observed in normal and failing human hearts, suggesting a possible role in cardiovascular homeostasis. Changes in plasma apelin concentrations in relation to heart failure have been described in small studies with conflicting results. Our aim was to evaluate plasma apelin concentrations in a large cohort of patients with chronic heart failure (CHF) across a broad spectrum of disease severity. Method and results: Plasma apelin concentrations were measured in 202 patients with CHF secondary to left ventricular systolic dysfunction and 22 age-matched controls. Plasma apelin concentrations were significantly lower in patients with CHF, irrespective of NYHA class, ejection fraction or aetiology when compared to age-matched controls (0.85 [0.53 -2.04] versus 3.76 [0.85 -5.13] ng/ml, p < 0.001). Apelin concentrations were correlated with peak VO 2 and right ventricular ejection fraction, but not with age, sex, body mass index, renal function or NT-proBNP concentrations. Conclusions: Plasma apelin concentrations are decreased in patients with CHF. The Apelin-APJ signaling pathway may be a potentially important mediator in the pathophysiological processes of heart failure and may therefore have potential therapeutic implications.

Serum level of apelin-13 negatively correlated with NT-proBNP in heart failure patients

“…The most important finding from our data is the negative, very strong correlation between serum levels of apelin-13 and NT-proBNP, which is in contradiction with other previous results [15], but in agreement with other scientific researches that showed lower apelin level in advanced heart failure, as well as with the theory that this decrease of serum apelin is negatively influenced by the course of the disease. Our findings showed that the Low apelin-13 group has higher NT-proBNP levels and also contains all the patients in NYHA IV class heart failure, 71% of the acute HF patients, and 7 of 8 patients who died before follow-up.…”

“…To our knowledge, there are no differences reported so far between genders, but already published studies either have a limited number of female subjects [15,[37][38][39], or the research focused mainly on male subjects [13,40]. The fact that there were no differences between genders other than apelin-13 level, NYHA class and LV mass and that apelin-13 was weakly correlated with LV mass when all subjects were analyzed (patients and controls) (Spearman's rho 0.28, p=0.023) give grounds for further research.…”

“…The plasmatic level of apelin is known to progressively decrease during the course of heart failure after an initial rise in the early stages of the disease [15]. These dynamics are considered to be an attempt to compensate and increase the contractile force of the failing heart [22], but these effects are progressively altered in the course of heart failure.…”

“…It is the most potent endogenic positive inotropic agent and is a positive regulator of angiotensin converting enzyme type 2, and so it is a RAAS antagonist [12,13]. Experimental studies conducted so far have attributed apelin a protective role on the cardiovascular system, but also on the nervous system, liver, pancreas and kidneys [14][15][16]. It seems to be a guardian of the living organism, human or animal, which regulates basic functions of the systems and tissues, helps in the process of recovery after an injury and appears to delay the onset of diseases.…”

The apelin receptor APJ: journey from an orphan to a multifaceted regulator of homeostasis

“…Yet its role is undetermined, as conflicting evidence has been found in KO studies, indicating both antagonistic and inducing roles for apelin in atherosclerotic formation (Hashimoto et al 2007. During heart failure, plasma apelin levels rise in the early stages of disease and stabilise or lower as the condition develops (Chen et al 2003, Chong et al 2006, Miettinen et al 2007). However, APJ mRNA is decreased in the weakened and enlarged heart of humans with idiopathic dilated cardiomyopathy (Foldes et al 2003).…”