# The Role of the Apelin Receptor in the Pathophysiology of Pulmonary Arterial Hypertension

## TL;DR

The apelin receptor (APJ) helps improve lung artery health and reduce disease progression in pulmonary arterial hypertension.

## Contribution

This review highlights APJ as a promising therapeutic target for pulmonary arterial hypertension.

## Key findings

- Activation of APJ improves endothelial function and reduces vascular remodeling in PAH.
- APJ reduces pulmonary vascular resistance and right ventricular hypertrophy.
- APJ agonists face pharmacokinetic limitations that hinder their clinical use.

## Abstract

What are the main findings?
Activation of the apelin receptor (APJ) is associated with improved endothelial homeostasis in pulmonary arterial hypertension.Activation of the apelin receptor (APJ) attenuates vascular remodeling in pulmonary arterial hypertension.

Activation of the apelin receptor (APJ) is associated with improved endothelial homeostasis in pulmonary arterial hypertension.

Activation of the apelin receptor (APJ) attenuates vascular remodeling in pulmonary arterial hypertension.

What are the implications of the main findings?
APJ reduces vascular tone and emerges as a promising therapeutic target in pulmonary arterial hypertension.APJ reduces pulmonary vascular resistance and attenuates right ventricular hypertrophy in pulmonary arterial hypertension.

APJ reduces vascular tone and emerges as a promising therapeutic target in pulmonary arterial hypertension.

APJ reduces pulmonary vascular resistance and attenuates right ventricular hypertrophy in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by endothelial dysfunction, vascular remodeling, and a sustained increase in pulmonary vascular resistance, causing cardiopulmonary damage. The apelin receptor (APJ), a member of the G protein-coupled receptor family, has emerged as an essential modulator of vascular homeostasis. Clinical and preclinical studies have demonstrated that its activation exerts beneficial effects on the progression of PAH. Its main actions include the restoration of endothelial function, reactivation of the BMPR2/SMAD axis, induction of nitric oxide-mediated vasodilation, inhibition of autophagy and the migration of the pulmonary artery smooth muscle cells (PASMCs). Furthermore, its expression and functionality are modulated by epitranscriptomic mechanisms, particularly by microRNAs involved in the post-transcriptional regulation of key genes for vascular homeostasis. These findings position the APJ as a relevant therapeutic target in PAH. However, the clinical application of its agonists still faces pharmacokinetic limitations that restrict their therapeutic use. Therefore, the aim of this review is to gather current information on APJ in the pathophysiology of PAH and focus attention on its potential as a therapeutic target.