Bridging the gap: combining GPCR-based drug discovery with iPSC-based cardiovascular disease modeling in a dish.

G protein-coupled receptor (GPCR) signalling plays a key role in the regulation of cardiovascular function, and in many cases, dysregulation of these events is a critical driver of disease progression. Drugs modulating GPCRs including β-blockers and angiotensin receptor blockers (ARBs) have served as largely symptomatic treatments spanning across several cardiovascular diseases. However, with few exceptions, most patients are treated with the same drugs in the same order regardless of etiology, often affecting disease progression. Thus, moving towards more personalized approaches to treating patients might improve outcomes. Over the past two decades, advances in induced pluripotent stem cell (iPSC)-derived cells have been transformative in accelerating our understanding of cardiovascular cell signalling in a patient-specific manner. In this review, we focus on how iPSC-derived cardiac models have increased our understanding of GPCR signalling in the context of cardiovascular disease, how these models have been used to investigate responses to clinically used drugs, and how these approaches might translate to the development of more personalized approaches and novel GPCR-targeting drugs.