Modulation of the apelin/APJ system in heart failure and atherosclerosis in man

Abstract

Background and purpose: The aim of this study was to determine whether the apelin/APJ system is altered in human cardiovascular disease by investigating whether the expression of apelin or its receptor is altered at the protein level. Experimental approach: Radioligand binding studies were used to determine apelin receptor density in human cardiac tissues. Apelin peptide levels in cardiovascular tissues were determined by radioimmunoassay. In vitro pharmacology was used to assess vasoactive properties of apelin in human coronary artery. Localization of apelin and its receptor in coronary artery was determined using immunohistochemistry. Key results: Apelin receptor density was significantly decreased in left ventricle from patients with dilated cardiomyopathy or ischaemic heart disease compared with controls, but apelin peptide levels remained unchanged. Apelin was up-regulated in human atherosclerotic coronary artery and this additional peptide localized to the plaque, colocalizing with markers for macrophages and smooth muscle cells. Apelin potently constricted human coronary artery. Conclusions and implications:We have detected changes in the apelin/APJ system in human diseased cardiac and vascular tissue. The decrease in receptor density in heart failure may limit the positive inotropic actions of apelin, contributing to contractile dysfunction. The contribution of the increased apelin levels in atherosclerotic coronary artery to disease progression remains to be determined. These data suggest a potential role for the apelin/APJ system in human cardiovascular disease.

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

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

“…In vascular diseases, the expression of apelin is up-regulated in the atherosclerosis of human coronary artery (Pitkin et al 2010). 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.…”

Apelin: an antithrombotic factor that inhibits platelet function

“…These molecules play an important role in the development and progression of atherosclerosis and the formation of occlusive thrombi. 4 Apelin and its cognate receptor APJ were shown to be involved in a number of physiological and pathophysiological conditions, 5 and their levels are altered in atherosclerotic coronary arteries, 6 in aortic valve stenosis, 7 and during acute myocardial infarction and angina. [8][9][10] All these observations raise the possibility that apelin signaling pathways play a role in the physiopathology of vascular disease.…”