Requirement of Apelin-Apelin Receptor System for Oxidative Stress-Linked Atherosclerosis

Abstract

The recently identified endogenous peptide apelin and its specific apelin receptor (APJ) are currently being considered as potential regulators in vascular tissue. Previously, we reported apelin mediates phosphorylation of myosin light chain and elicits vasoconstriction in vascular smooth muscle. In this study, physiological roles of the apelin-APJ system were investigated on atherosclerosis. In APJ and apolipoprotein E double-knockout (APJ ؊/؊ ApoE ؊/؊ ) mice fed a high-cholesterol diet, atherosclerotic lesions were dramatically reduced when compared with APJ Apelin receptor (APJ) is a G-protein-coupled receptor with seven transmembrane domains, and its endogenous ligand, apelin has been recently identified.1,2 The structures of APJ and apelin are highly conserved among species, and both are highly expressed in the cardiovascular system. 3,4 In the vascular system, APJ and apelin are known to be expressed in endothelium and vascular smooth muscle cells (VSMCs). Histological studies in rat show that the VSMCs of the medial layer of the aorta and pulmonary artery display intense staining for APJ-like immunoreactivity. 4 The vascular actions of apelin-APJ system may be complex. Under physiological conditions, the apelin-APJ system shows transient hypotension. The baseline blood pressure of APJ and angiotensin-type 1 receptor doubleknockout mice was significantly elevated compared with that of angiotensin-type 1 receptor knockout mice, 5 although APJ knockout (APJ Ϫ/Ϫ ) mice did not show any significant changes in cardiovascular parameters. In spontaneously hypertensive rats, APJ and apelin expression in both heart and aorta were markedly depressed compared with Wistar-Kyoto rats. 6 In aortae from type 2 diabetic db/db mice, APJ and apelin expression were

Plasma apelin levels in obstructive sleep apnea and the effect of continuous positive airway pressure therapy

“…In our study, the dyslipidaemia remained unchanged with CPAP therapy and therefore contributed insignificantly to the changes reported in apelin levels. However, the APJ/apelin system appears to have a role in the development of hypercholesterolaemia-associated atherosclerosis (Hashimoto et al 2007). Therefore, although elevated plasma apelin levels in untreated OSA may be beneficial in terms of glucose homeostasis (and hypertension -see below), there are putative deleterious consequences for oxidative stress-linked vascular disease, which warrant further investigation.…”

Reduced Apelin Levels in Stable Angina

“…More recent reports have indicated that this peptide has been down-regulated in subjects with acute heart failure (5). Furthermore, apelin also induced vascular smooth muscle cell proliferation, which was inhibited by superoxide dismutase or diphenylene iodonium; APJ deficiency is preventative against oxidative stress-linked atherosclerosis; the apelin-APJ system is a mediator of oxidative stress in vascular tissue (6), and thus we speculated it to have some relationship with arterial atherosclerosis. …”

Mechanisms by which diabetes increases cardiovascular disease

“…The role of leptin in atherogenesis is currently controversial as leptin (ob/ob) or leptin receptor (db/db) deficiency in Apoe −/− mice has resulted in attenuation of plaque formation [53] or increased atherogenesis [54]. Inactivating of the apelin receptor (APJ) in Apoe −/− mice resulted in reduced lesion size and oxidative stress, suggesting a role for apelin in atherogenesis [55].…”