Vascular effects of apelin: Mechanisms and therapeutic potential

Abstract

Apelin is a vasoactive peptide and is an endogenous ligand for APJ receptors, which are widely expressed in blood vessels, heart, and cardiovascular regulatory regions of the brain. A growing body of evidence now demonstrates a regulatory role for the apelin/APJ receptor system in cardiovascular physiology and pathophysiology, thus making it a potential target for cardiovascular drug discovery and development. Indeed, ongoing studies are investigating the potential benefits of apelin and apelin-mimetics for disorders such as heart failure and pulmonary arterial hypertension. Apelin causes relaxation of isolated arteries, and systemic administration of apelin typically results in a reduction in systolic and diastolic blood pressure and an increase in blood flow. Nonetheless, vasopressor responses and contraction of vascular smooth muscle in response to apelin have also been observed under certain conditions. The goal of the current review is to summarize major findings regarding the apelin/APJ receptor system in blood vessels, with an emphasis on regulation of vascular tone, and to identify areas of investigation that may provide guidance for the development of novel therapeutic agents that target this system.

Long-term treatment with acylated analogues of apelin-13 amide ameliorates diabetes and improves lipid profile of high-fat fed mice

“…Both the fatty acid apelin analogues had positive effect on reducing circulating triglycerides, LDL-cholesterol as well as increasing HDL-cholesterol. Cardiovascular benefits of apelin, including reduction of blood pressure are well established [ 51 ] and further studies would be worthwhile to explore such actions in the present context. Once daily administration of the GLP-1 mimetic, liraglutide replicated all of the benefits of apelin-13 analogues but it failed to completely improve lipid profile in high-fat fed mice as shown previously in our lab [ 38 ].…”

Cardiovascular response to small-molecule APJ activation

“…The vascular effects caused by modulation of the apelin/APJ axis are complex. Apelin can act as a potent vasodilator or vasoconstrictor, depending on the underlying state of the vascular bed (12,(56)(57)(58). APJ is expressed in both endothelial and smooth muscle cells within the vessel wall, and apelin's vasodilatory properties are driven, in part, by endothelium-derived increases in NO bioavailability (58)(59)(60)(61)(62)(63).…”

Expression profile analysis of Differentially Expressed Genes in Human Coronary Artery Endothelial Cells Induced by Serum from Kawasaki Disease: A preliminary study

“…TGF-β pathway is involved in in ammation and tissue remodeling mediated by endothelial cells, and immune activation, which support the importance of TGF-βpathway in KD occurrence and outcomes [15,16].CD34 positive cells with enhanced adhesive and homing properties facilitates immune cells homing to the in ammatory sites and mediates in ammatory and immune responses [17].CXCL1, as the chemokine ligand, presents on endothelial surface and mediates immune responses by recruitment of neutrophils and monocytes [18,19].APLN(apelin) is a vasoactive peptide and an endogenous ligand for APJ receptors. APLN/APJ receptor system plays a vital role in regulation of vascular function, including vascular tone, angiogenesis, proliferation, and permeability [20,21].In addition, APLN/APJ system also mediates the anti-in ammatory effects of 1,25(OH)2D3 by reduction of pro-in ammatory mediators and adhesion molecules in LPS-stimulated macrophages [22]. PITX2 plays an important role in regulating the differentiation of endothelium and angiogenesis [23,24].Although these studies provide insights into these biomarkers involved in regulation of cardiovascular and immune system, it is yet unknown whether these alterations can be considered as potential indicators for prevention and treatment of coronary artery damage in KD, which needs further investigations.…”