Pulmonary hypertension and associated heart failure: New insights on emerging signalling pathways

Pulmonary hypertension associated with left heart disease (PH-LHD) represents the hemodynamic condition at rest resulting from pathologies that affect the left ventricle and/or the left atrium. Among the left heart diseases, heart failure is the most frequent cause of PH. PH-LHD is the most common cause of PH, accounting for 65-80% of diagnoses. Several drugs targeting specific signalling pathways involved in the pulmonary remodelling in PH-LHD, including nitric oxide, MAP kinase and endothelin-1, have been tested in randomized clinical trials (RCTs), with disappointing results in terms of efficacy and safety. Therefore, PH-LHD still remains orphan of specific therapies able to counteract the pre- and post-capillary remodelling of the pulmonary circulation. In this article, we will discuss the pathophysiology and molecular mechanisms of PH-LHD. We will focus on the emerging signalling pathways involved in the pathophysiology of PH-LHD that could suggest novel molecular targets for the treatment of this condition.