Adenosine A2A Receptor as a Target of Treatment for Pulmonary Arterial Hypertension - Abstract
Pulmonary arterial hypertension (PAH) is a rare condition characterized by small pulmonary artery remodeling that leads to chronic precapillary pulmonary hypertension, elevated pulmonary vascular resistance, and right heart failure. Therapeutic options for PAH remain limited despite the introduction of prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase 5 inhibitors within the last 15 years. Predominantly, these interventions address the endothelial and vascular dysfunctions associated with PAH, and simply delay progression of the disease rather than offer a cure. To improve treatment efficacy, emerging approaches are focusing on the pro-proliferative phenotype as the target. This phenotype underpins pulmonary vascular remodeling in the lung and contributes to impaired circulation and right heart failure. Several new targets have been investigated and validated in experimental PAH models. Further, the adenosinergic system, specifically the adenosine A2A receptor, is potentially a novel and efficient approach for PAH treatment. Herein, we provide a review of the effects of adenosine on the cardiopulmonary system, focusing on the contribution of the A2A receptor as a pharmacological target that induces pulmonary vasodilatation and cardioprotection in experimental PAH models.