Apelin/APJ system: a promising therapy target for hypertension

Abstract

Apelin is a recently described endogenous peptide and its receptor APJ, is a member of the G protein-coupled receptors family. Apelin and APJ are widely distributed in central and peripheral tissues exert important biological effects on cardiovascular system. Recent studies have suggested that apelin/APJ system involves in decreasing the blood pressure and have a close relationship with hypertension, presumably, pathophysiology of hypertension as well. Such as, apelin/APJ system may be concerned in hyperfunction of the sympathetic nervous system, renin-angiotensin-aldosterone system, endothelial injury, excessive endothelin, sodium retention, vascular remodeling, insulin resistance elicit hypertension, as well as in hypertension-induced organ damaged. Meanwhile, on the ground of the variation of apelin level in hypertension therapeutic process and combining with the recently researches on APJ agonist and antagonist, we could infer that apelin/APJ system would be a promising therapeutic target for hypertension and other cardiovascular disease in the future. However, the role of apelin on these pathogenic conditions was not consistent, consequently, the contradictory role of apelin on these pathogenesis of hypertension would be discussed in this article.

Apelin-13 promotes cardiomyocyte hypertrophy via PI3K-Akt-ERK1/2-p70S6K and PI3K-induced autophagy

“…At the early stage of cardiomyopathy, myocardial hypertrophy is a compensatory function, but ultimately, this can lead to heart failure and has become a significant independent risk factor of cardiovascular disease [47]. At present, myocardial hypertrophy occurs mainly due to mechanical load [1][2][3] and neurohumoral factors [4][5][6]. The earliest hemodynamic effect in the pathogenesis of myocardial hypertrophy has been identified.…”

“…Apelin-13 that acts as a mature apelin peptide, is the most commonly studied and has comparable affinity and agonist activity with the native apelin receptor in human tissues [3]. Apelin-13 is the predominant apelin isoform in human cardiac tissue [4] and plays a protective role in myocardial contraction, blood pressure regulation [5,6], myocardial injury [7], and so on. In addition to its protective role [8][9][10], apelin-13 promotes vascular smooth muscle cell (VSMC) proliferation [11][12][13] and endothelial cell (EC) adhesion [14][15][16].…”

Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases

“…It was discovered in 1993 via homology cloning [164,165] . Apelin-13/APJ system has been identified as a potential therapeutic target for hypertension [166] and atherosclerosis [167] . Our laboratory has demonstrated that apelin-13 induced proliferation of vascular smooth muscle cells [66,168] and rat bone marrow-derived mesenchymal stem cells [169] through the Jagged-1/Notch3, cyclin D1 and AKT/ GSK3β/cyclin D1 pathways.…”

Apelin/APJ system: A novel therapeutic target for oxidative stress-related inflammatory diseases (Review)

“…On the one hand, vascular endothelial shear stress, oxidative stress, inflammation and other factors can alter apelin expression; on the other hand, apelin has an impact on insulin sensitivity and cardiovascular function, exerting anti-inflammatory and antioxidant effects, acting as an adipokine (102). In addition, the overproduction of ROS can lead to a series of inflammatory reactions, and apelin can regulate the production of ROS; thus,there is a close link between apelin, oxidative stress and inflammation.…”