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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Publikationen des W. G. Kerckhoff-Instituts     Display Documents



ID: 474517.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
[Update: Preclinical developments for the treatment of pulmonary arterial hypertension]
Authors:Janssen, W.; Ghofrani, H. A.; Weissmann, N.; Grimminger, F.; Schermuly, R. T.
Date of Publication (YYYY-MM-DD):2009
Title of Journal:Dtsch Med Wochenschr
Volume:134 Suppl 5
Start Page:S157
End Page:9
Audience:Not Specified
Abstract / Description: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.
Free Keywords:Animals; Cyclic Nucleotide Phosphodiesterases, Type 5/antagonists & inhibitors; Disease Progression; Epoprostenol/pharmacology/therapeutic use; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use; Hypertension, Pulmonary/*drug therapy/pathology; NADPH Oxidase/metabolism; Pancreatic Elastase/antagonists & inhibitors; Phosphodiesterase I/antagonists & inhibitors; Protein-Tyrosine Kinases/antagonists & inhibitors; Pulmonary Artery/drug effects/pathology/*physiopathology; Reactive Oxygen Species/metabolism; Receptors, Endothelin/antagonists & inhibitors; Serotonin Antagonists/therapeutic use; Signal Transduction/drug effects; Vasoconstriction/drug effects; Vasodilator Agents/therapeutic use; rho-Associated Kinases/antagonists & inhibitors
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Max-Planck-Institut fur Herz- und Lungenforschung, Bad Nauheim.
Identifiers:ISSN:1439-4413 (Electronic) 0012-0472 (Linking)
URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=..
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