Current Drug Targets and Future Therapy of Pulmonary Arterial Hypertension

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Abstract:

During the last few decades, we have witnessed major improvements in the therapy of pulmonary arterial hypertension (PAH). PAH is characterized by abnormal remodeling of the pulmonary artery (PA) and increased PA pressures, resulting in a high premature mortality. Intravenous epoprostenol was the first effective approach toward improving the symptoms and survival of PAH patients. New prostanoids have also exhibited substantial clinical benefits; however, their long-term effects are under investigation. Endothelin-receptor antagonists and sildenafil have increased the lineup of therapeutic options against PAH. Combination therapy using these drugs is promising and is currently undergoing scrutiny in large clinical trials. An extensive analysis of the molecular mechanisms of PAH will produce novel targeted therapies. Most of the promising molecules target the inflammatory and proliferative processes underlying pathological PA remodeling. Interestingly, drugs used for other diseases, such as statins, Rho-kinase inhibitors, imatinib mesylate, may control the pathological vascular remodeling of PAH. Gene and cell therapy using vectors expressing prostacyclin synthase, endothelial nitric oxide synthase, or vascular endothelial growth factor are also promising strategies. However, the efficacy and safety of these approaches should be further tested in clinical trials. Genetic studies revealed some crucial genetic dispositions of familial PAH, although their pathobiological roles have not yet been fully clarified. Collaboration for integrated research will address these issues and generate greater clinical benefits for PAH patients.

Keywords: Pulmonary arterial hypertension; endothelin; gene therapy; inflammation; proliferation; prostacyclin; sildenafil; treatment

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986707780059562

Affiliations: Division of Cardiovascular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.

Publication date: March 1, 2007

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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