Prokineticin receptors in cardiovascular function: foe or friend?

Prokineticins are small secreted bioactive peptides, comprising two classes: prokineticin-1 and prokineticin-2. They exert their biological activity by binding to two G-protein-coupled receptors: prokineticin receptor (PKR) 1 and 2. Recent data have demonstrated that PKR1 induces postnatal neovasculogenesis by activating adult epicardial-derived progenitor cell differentiation, whereas myocardial PRK2 signaling confers detrimental actions on cardiomyocytes, leading to dilated cardiomyopathy and release of an unknown paracrine factor to induce capillary fenestration and vascular leakage. The knowledge gained from these studies leads to a model in which PKR1 and PKR2 signaling exert opposing actions in heart physiology and pathophysiology and facilitate the discovery of specific agonists and antagonists targeting PKR1 and PKR2 for possible use in treatment of cardiovascular diseases.