Elsevier

Clinica Chimica Acta

Volume 413, Issues 3–4, 18 February 2012, Pages 406-410
Clinica Chimica Acta

Invited critical review
Apelin in acute myocardial infarction and heart failure induced by ischemia

https://doi.org/10.1016/j.cca.2011.11.021Get rights and content

Abstract

Apelin is a recently isolated novel endogenous ligand for the angiotensin-like 1 receptor (APJ). Initial experiments in animal models indicate that the cardiovascular system is the main target of the apelin–APJ system. Apelin plays an opposite role to the renin-angiotensin-aldosterone system as a compensatory mechanism. It is reduced in patients with heart failure, also of ischemic origin. However, only animal studies concern the role of the apelin–APJ system in myocardial ischemia. Less is known about the function of this adipokine in an acute phase of myocardial infarction in human. The apelin–APJ system could perhaps be involved in myocardial protection during acute myocardial ischemia. In the current review we have summarized recent data concerning the role of apelin in acute myocardial infarction and heart failure induced by ischemia.

Highlights

► Only animal studies concern the role of apelin–APJ system in myocardial ischemia. ► Less is known about apelin function in acute phase of myocardial infarction in human. ► Apelin–APJ system could be involved in myocardial protection in acute ischemia. ► Data concerning apelin role in acute myocardial infarction and heart failure have been reviewed.

Introduction

Apelin belongs to the adipokines − a term used to denote cytokines, growth factors, and other proteins produced and secreted by adipocytes. These factors are also called adipocytokines [1]. This does not imply that expression and production of such factors is restricted to adipocytes as most of these factors are also produced by a variety of other cell types. The term often refers to leptin and adiponectin, which are secreted by the adipocytes of adipose tissue. A variety of other factors are also released by adipose tissue in vitro and in vivo and these have been also termed collectively as adipokines or adipocytokines (TNF-alpha, IL-6, leptin, omentin, visfatin, adipsin, resistin, apelin, retinol binding protein rbp4) [2].

Section snippets

Overview of apelin physiology and pathophysiology

In 1993 O'Dowd et al. identified an endogenous ligand for the angiotensin-like 1 receptor (APJ) [3]. This is a ligand for one of the earliest, so called “orphan” G-protein-coupled receptors (GPCRs). GPCRs represent the largest group of transmembrane proteins responsible for transduction of a diverse array of extracellular signals. Recent progress in genome research revealed a total of about 300 GPCRs [4]. Approximately 140 of these novel GPCRs do not bind any known endogenous ligand and are

Animal studies

The majority of experimental data regarding the role of apelin in cardiovascular system has been conducted in rodents. Sparse studies used other animals. Del Ry et al. have been used a wild boar (Sus scrofa) model to establish its genoma sequence for apelin for future applications of molecular biology studies [20]. While other researchers, on the canine model, have investigated the influence of apelin on changes in intracellular sodium current, which may contribute to the apelin inotropic

Animal studies

The role of apelin−APJ in the pathogenesis of heart failure has received a great attention. Szokodi et al. were the first group to report downregulation of apelin mRNA in cardiac myocytes under cyclic stretch in vitro and in ventricular myocardium from two rat models of hypertensive heart failure [11]. In animal models of heart failure the expression of apelin and APJ is increased or maintained in animals with left ventricular hypertrophy and compensated heart failure, but downregulated in

Apelin as a therapeutic target in heart failure?

Japp and co-workers were the first to demonstrate an influence of acute administration of apelin-36 infusion on human cardiovascular system in vivo [51]. Apelin was injected into peripheral artery as well as intracoronary bolus was given in order to measure coronary blood flow and LV contractility and pressures. Intravenous infusion of apelin was given for the systemic hemodynamic study. They were able to demonstrate peripheral and coronary vasodilatation, improvement of myocardial

Conclusions

In summary, available data from animal and human studies suggest that apelin–APJ system is:

  • 1.

    upregulated in response to hypoxia/ischemia

  • 2.

    maintained or augmented in chronic pressure overload and the early stages of heart failure

  • 3.

    essentially downregulated in severe heart failure.

The studies confirm the validity of apelin as a new adipokine of cardiovascular importance. Still available data do not give responses to all questions. Existing studies provide sparse data. Experimental and clinical

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