Acute Cardiovascular Effects of Apelin in Humans

Abstract

Background-Apelin, the endogenous ligand for the novel G protein-coupled receptor APJ, has major cardiovascular effects in preclinical models. The study objectives were to establish the effects of acute apelin administration on peripheral, cardiac, and systemic hemodynamic variables in healthy volunteers and patients with heart failure. Methods and Results-Eighteen patients with New York Heart Association class II to III chronic heart failure, 6 patients undergoing diagnostic coronary angiography, and 26 healthy volunteers participated in a series of randomized, double-blind, placebo-controlled studies. Measurements of forearm blood flow, coronary blood flow, left ventricular pressure, and cardiac output were made by venous occlusion plethysmography, Doppler flow wire and quantitative coronary angiography, pressure wire, and thoracic bioimpedance, respectively. Intrabrachial infusions of (Pyr 1 )apelin-13, acetylcholine, and sodium nitroprusside caused forearm vasodilatation in patients and control subjects (all PϽ0.0001). Vasodilatation to acetylcholine (Pϭ0.01) but not apelin (Pϭ0.3) or sodium nitroprusside (Pϭ0.9) was attenuated in patients with heart failure. Intracoronary bolus of apelin-36 increased coronary blood flow and the maximum rate of rise in left ventricular pressure and reduced peak and end-diastolic left ventricular pressures (all PϽ0.05). Systemic infusions of (Pyr 1 )apelin-13 (30 to 300 nmol/min) increased cardiac index and lowered mean arterial pressure and peripheral vascular resistance in patients and healthy control subjects (all PϽ0.01) but increased heart rate only in control subjects (PϽ0.01). Conclusions-Acute apelin administration in humans causes peripheral and coronary vasodilatation and increases cardiac output. APJ agonism represents a novel potential therapeutic target for patients with heart failure. (Circulation.

Adipokines and cardiovascular disease: A comprehensive review

“…Acute administration of apelin in people with heart failure induced an increase of coronary blood flow, decrease in blood pressure and increase in cardiac output 70 . Further studies demonstrated an increase in cardiac index and ejection fraction that remained increased during a six-hour infusion, but heart rate increase occurred only during the first hour of the infusion 71 .…”

Apelin-36 Modulates Blood Glucose and Body Weight Independently of Canonical APJ Receptor Signaling

“…Thus, our discovery of an apelin variant that uncouples cardiovascular from metabolic activity suggests the possibility of developing apelin peptides with the ability to treat metabolic disease without impacting cardiovascular function. In addition to lacking cardiovascular activity, such a candidate therapeutic would also need to exhibit a longer half-life than wild-type apelin-36 to allow for a once daily or less frequent dosing interval (15).…”

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

“…These assumptions were made after observing the effects of experimental iv administration of apelin to animals and humans with heart failure: it acts as a potent inotrope and increases the contractility of the heart, the ejection fraction and the cardiac output and lowers the left ventricle diastolic pressure . These effects were described initially on isolated hearts on which apelin exerted a clear inotropic effect, especially on failing myocardium [23,24], and then were reproduced on healthy and heart failure human volunteers [25,26]. All these scientific results are proof of the beneficial role of apelin in the human body and in particular in the functioning of the cardiovascular system but it suggests its limited protective effect until it is overcome by the injurious molecular pathway and its tissular and serum level begin to fall.…”