Pulmonary
arterial hypertension is a rare and devastating disease
characterized by an abnormal chronic increase in pulmonary arterial
pressure above 20 mmHg at rest, with a poor prognosis if not treated.
Currently, there is not a single fully effective therapy, even though
a dozen of drugs have been developed in the last decades. Pulmonary
arterial hypertension is a multifactorial disease, meaning that several
molecular mechanisms are implicated in its pathology. The main molecular
pathways regulating the pulmonary vasomotor toneendothelin,
nitric oxide, and prostacyclinare the most biologically and
therapeutically explored to date. However, drugs targeting these pathways
have already found their limitations. In the last years, translational
research and clinical trials have made a strong effort in suggesting
and testing novel therapeutic strategies for this disease. These approaches
involve targeting the main molecular pathways with novel drugs, drug
repurposing for novel targets, and also using combinatorial therapies.
In this review, we summarize current strategies and drugs targeting
the endothelin, nitric oxide, and prostacyclin pathways, as well as,
the emerging new drugs proposed to cope with vascular remodelling,
metabolic switch, perivascular inflammation, epigenetic modifications,
estrogen deregulation, serotonin, and other neurohumoral mechanisms
characteristic of this disease. Nowadays, pulmonary arterial hypertension
remains an incurable disease; however, the incoming new knowledge
makes us believe that new promising therapies are coming to the clinical
arena soon.