| Title | [Update: Preclinical developments for the treatment of pulmonary arterial hypertension] | | Author(s) | Janssen W, Ghofrani HA, Weissmann N, Grimminger F, Schermuly RT | | Institution | Max-Planck-Institut für Herz- und Lungenforschung, Bad Nauheim. | | Source | Dtsch Med Wochenschr 2009 Aug.:S157-9. | | MeSH | Animals
Cyclic Nucleotide Phosphodiesterases, Type 5
Disease Progression
Epoprostenol
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypertension, Pulmonary
NADPH Oxidase
Pancreatic Elastase
Phosphodiesterase I
Protein-Tyrosine Kinases
Pulmonary Artery
Reactive Oxygen Species
Receptors, Endothelin
Serotonin Antagonists
Signal Transduction
Vasoconstriction
Vasodilator Agents
rho-Associated Kinases
| | Abstract | 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. | | Language | ger | | Pub Type(s) | English Abstract
Journal Article
Review
| | PubMed ID | 19718604 |
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