The current approach into signaling pathways in pulmonary arterial hypertension and their implication in novel therapeutic strategies.

Many mediators and signaling pathways, with their downstream effectors, have been implicated in the pathogenesis of pulmonary hypertension. Currently approved drugs, representing an option of specific therapy, target NO, prostacyclin or ET-1 pathways and provide a significant improvement in the symptomatic status of patients and a slower rate of clinical deterioration. However, despite such improvements in the treatment, PAH remains a chronic disease without a cure, the mortality associated with PAH remains high and effective therapeutic regimens are still required. Knowledge about the role of the pathways involved in PAH and their interactions provides a better understanding of the pathogenesis of the disease and may highlight directions for novel therapeutic strategies for PAH. This paper reviews some novel, promising PAH-associated signaling pathways, such as RAAS, RhoA/ROCK, PDGF, PPAR, and TGF, focusing also on their possible interactions with well-established ones such as NO, ET-1 and prostacyclin pathways.