Targeting the elabela/apelin-apelin receptor axis as a novel therapeutic approach for hypertension

Abstract

Hypertension is the leading risk factor for global mortality and morbidity and those with hypertension are more likely to develop severe symptoms in cardiovascular and cerebrovascular system, which is closely related to abnormal renin–angiotensin system and elabela/apelin–apelin receptor (APJ) axis. The elabela/apelin–APJ axis exerts essential roles in regulating blood pressure levels, vascular tone, and cardiovascular dysfunction in hypertension by counterbalancing the action of the angiotensin II/angiotensin II type 1 receptor axis and enhancing the endothelial nitric oxide (NO) synthase/NO signaling. Furthermore, the elabela/apelin–APJ axis demonstrates beneficial effects in cardiovascular physiology and pathophysiology, including angiogenesis, cellular proliferation, fibrosis, apoptosis, oxidative stress, and cardiovascular remodeling and dysfunction during hypertension. More importantly, effects of the elabela/apelin–APJ axis on vascular tone may depend upon blood vessel type or various pathological conditions. Intriguingly, the broad distribution of elabela/apelin and alternative isoforms implicated its distinct functions in diverse cardiac and vascular cells and tissue types. Finally, both loss-of-function and gain-of-function approaches have defined critical roles of the elabela/apelin–APJ axis in reducing the development and severity of hypertensive diseases. Thus, targeting the elabela/apelin–APJ axis has emerged as a pre-warning biomarker and a novel therapeutic approach against progression of hypertension, and an increased understanding of cardiovascular actions of the elabela/apelin–APJ axis will help to develop effective interventions for hypertension. In this review, we focus on the physiology and biochemistry, diverse actions, and underlying mechanisms of the elabela/apelin–APJ axis, highlighting its role in hypertension and hypertensive cardiovascular injury and dysfunction, with a view to provide a prospective strategy for hypertensive disease therapy.