Targeting Drugs to APJ Receptor: The Prospect of Treatment of Hypertension and Other Cardiovascular Diseases

Abstract

The APJ is a class A, rhodopsin-like G protein-coupled receptor (GPCR) with high sequence similarity to the angiotensin receptor AT1. APJ has been shown to be widely expressed in humans tissues, including the central nervous system, cardiovascular system, adipocytes and others. APJ plays an important role in the occurrence and development of cardiovascular and metabolic diseases including atherosclerosis (AS), coronary heart disease (CAD), heart failure(HF), pulmonary arterial hypertension (PAH), myocardial hypertrophy and atrial fibrillation, especially hypertension. Previous researchers found that apelin/APJ could induce vasodilation and then reduce blood pressure. Despite APJ is closely associated with many diseases, there are no drugs that can activate or inhibit APJ directly. In the current review, we have summarized recently reported peptides, small molecule agonists and antagonists targeting APJ. Given the role of apelin/APJ in hypertension and other cardiovascular diseases, we believe that the peptides and compounds based on APJ will be developed for treatment of these diseases.

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] .…”

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

“…Therefore, the apelin/APJ system has become one of the potential drug targets (94), and drugs targeting aplelin/APJ may apply to the treatment of several diseases.…”

“…Above the small molecules, a number of peptides based on apelin-13 has led to development of more potent and stable analogs targeted APJ (100). As showed in the review of Cao et al (94), the analogs of apelin may directly reduce blood pressure or by activating Akt-eNOS/NO pathway.…”

Apelin/APJ system: a novel promising therapy target for thrombotic diseases

“…Therefore, the apelin/APJ system may become new drug targets [9], and the drugs targeting at apelin/APJ may potentially be developed to treat the relevant diseases. Apelin is the endogenous ligand of APJ.…”

“…Elabela can also increase cardiac contractility and induce coronary vasodilation, which is similar to apelin. Besides these two peptide ligands, E339-3D6 and ML233, are the non-peptide agonists of APJ, while F13A is the natural antagonist isoform of APJ [9]. However, ML221 and ALX40-4C are the antagonists to APJ receptor [9].…”