JOURNAL ARTICLE
REVIEW

[Update: Preclinical developments for the treatment of pulmonary arterial hypertension]

W Janssen, H A Ghofrani, N Weissmann, F Grimminger, R T Schermuly
Deutsche Medizinische Wochenschrift 2009, 134 Suppl 5: S157-9
19718604
Pulmonary arterial hypertension is a life-threatening, vasculoproliferative disease of the lung, which is characterized by vasoconstriction and remodeling of small pulmonary arteries. Drugs for the treatment of PAH mainly address the increased vascular tone. Substances like prostacyclin, endothelin-receptor-antagonists and phosphodiesterase-5-inhibitors have been approved for the treatment of PAH and represent the current therapeutic options. The development of a causal treatment aiming a normalization of the vessel wall structure is the current focus of research. The key events in disease progression are represented by increased proliferation, migration and a resistance to apoptosis of pulmonary vascular cells. Therefore, new non-vasoactive drugs are investigated in relevant preclinical animal models of pulmonary arterial hypertension. Some of these substances, like tyrosine kinase inhibitors, elastase inhibitors and phosphodiesterase-1-inhibitors, could not only attenuate (anti-remodeling) but reverse (reverse-remodeling) the disease. Additionally, new vasodilators, like soluble guanylate cyclase stimulators and activators, addressing well-known and new signaling pathways are currently under investigation. Taken together, with increasing insight into the pathology of PAH, several novel drug targets and treatments have emerged which may improve the management of patients and which efficacy is currently addressed in preclinical studies and clinical trials.

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