Insights into the Expression, Structure, and Function of the Thromboxane A₂ Receptor in Vascular Biology

The thromboxane A₂ receptor is known for its role in platelet aggregation. In platelets, loss or gain-of-function of the thromboxane A₂ receptor may therefore lead to bleeding disorders or prothrombotic conditions. However, the thromboxane A₂ receptor is also expressed in many other cell types and tissues and is thought to contribute to a broad range of other pathophysiological processes, such as pulmonary hypertension and cancer cell metastasis. In endothelial cells, the thromboxane A₂ receptor is an important player in the pathogenesis of endothelial dysfunction, one of the main contributors to the development of hypertension and atherosclerosis-related diseases. In this review, we provide insight into the genomic structure and expression, protein structure and function of the thromboxane A₂ receptor, with a particular focus on vascular (patho)-physiology and recent findings regarding the involvement of thromboxane A₂ receptor signaling in the pathogenesis of endothelial dysfunction and cardiovascular disease. In addition, we provide an overview of clinically relevant polymorphisms within the thromboxane A₂ receptor gene (TBXA2R) and their influence on gene expression, protein structure, and receptor pathophysiology.