The role of P2Y6 receptor in the pathogenesis of cardiovascular and inflammatory diseases

The purinergic receptor P2Y₆ receptor (P2Y₆R) is a member of the G protein-coupled receptors (GPCR) family. P2Y₆R is widely expressed in various cell types and plays a critical role in physiological processes, where it is activated by extracellular uridine diphosphate (UDP) and mobilizes CA²⁺ via the G_αq/11 protein pathway. We have recently discovered the pathophysiological role of P2Y₆R in cardiovascular and inflammatory diseases, including inflammatory bowel disease and non-alcoholic fatty liver disease. Furthermore, we uncovered the redox-dependent internalization of P2Y₆R. In this review, we provide a comprehensive overview of the pathophysiological activity of P2Y₆R in cardiovascular and inflammatory diseases. Additionally, we discuss the concept of atypical internalization control of GPCRs, which may be applied in the prevention and treatment of intestinal inflammation and cardiovascular remodeling.

Cardiovascular disease; G protein-coupled receptors; Inflammation; Internalization; Non-alcoholic steatohepatitis.