PG F(2α) Receptor: A Promising Therapeutic Target for Cardiovascular Disease

Abstract

Prostaglandins (PGs), a group of key lipid mediators, are involved in numerous physiological and pathological processes including inflammation and cardiovascular homeostasis. Each PG acts on its specific and distinct cell surface G protein-coupled receptors (GPCRs) or peroxisome proliferator-activated receptors (PPARs). Prostaglandin F(2α) receptor (FP) is required for female reproductive function such as luteolysis and parturition. It has recently been implicated in blood pressure regulation, atherosclerosis and other inflammation-related disorders. The emerging role of FP in cardiovascular diseases is highlighted and potential therapeutic translation is discussed in the current review.

Keywords: FP receptor; atherosclerosis; hypertension; prostaglandin F2alpha.

Figure 1

Prostanoid biosynthesis and response pathway. AA, arachidonic acid; PLA₂, phospholipase A₂; PGHS1/2, prostaglandin G/H synthase 1 or 2, which contains both cyclooxygenases (COX) and peroxidase (POX) activities; PGIS, prostaglandin I₂ synthase; PGES, prostaglandin E₂ synthase; PGFS, prostaglandin F synthase; PGDS, prostaglandin D₂ synthase; TxS, thromboxane A₂ synthase; IP, prostaglandin I₂ receptor; EP, prostaglandin E₂ receptor; FP, prostaglandin F_2α receptor; DP, prostaglandin D₂ receptor; TP, thromboxane A₂ receptor.

Figure 2

Scheme of PGF_2α/FP pathway involved in pathogenesis of cardiovascular disease. Cardiac fibroblasts derived PGF_2α induces cardiac hypertrophy, fibrosis and arrhythmia through FP receptor in adjacent cardiomyocytes (CMs); PGF_2α stimulates renin release from juxtaglomerular granular cells (JGCs) by FP receptor in an autocrine fashion, and activate renin–angiotensin–aldosterone system (RAAS) to elevate blood pressure through enhancing salt/water reabsorption in kidney and constricting blood vessels directly via Angiotensin II (Ang II); PGF_2α promotes resistance artery constriction through FP in smooth muscle cells (SMCs), which eventually increases blood pressure and contributes to atherosclerosis; Activated RAAS also accelerates atherosclerosis. JGA, juxtaglomerular apparatus; AGT, angiotensinogen; ACE, angiotensin-converting enzyme; ALD, aldosterone.