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Novel Targets of Drug Treatment for Pulmonary Hypertension

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Abstract

Biomedical advances over the last decade have identified the central role of proliferative pulmonary arterial smooth muscle cells (PASMCs) in the development of pulmonary hypertension (PH). Furthermore, promoters of proliferation and apoptosis resistance in PASMCs and endothelial cells, such as aberrant signal pathways involving growth factors, G protein-coupled receptors, kinases, and microRNAs, have also been described. As a result of these discoveries, PH is currently divided into subgroups based on the underlying pathology, which allows focused and targeted treatment of the condition. The defining features of PH, which subsequently lead to vascular wall remodeling, are dysregulated proliferation of PASMCs, local inflammation, and apoptosis-resistant endothelial cells. Efforts to assess the relative contributions of these factors have generated several promising targets. This review discusses recent novel targets of therapies for PH that have been developed as a result of these advances, which are now in pre-clinical and clinical trials (e.g., imatinib [phase III]; nilotinib, AT-877ER, rituximab, tacrolimus, paroxetine, sertraline, fluoxetine, bardoxolone methyl [phase II]; and sorafenib, FK506, aviptadil, endothelial progenitor cells (EPCs) [phase I]). While substantial progress has been made in recent years in targeting key molecular pathways, PH still remains without a cure, and these novel therapies provide an important conceptual framework of categorizing patients on the basis of molecular phenotype(s) for effective treatment of the disease.

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Acknowledgments

We thank Dr. Sergei Snovida for helpful comments on the manuscript and Elfy Chiang for the graphic assistance.

Compliance with ethical standards

There are no conflicts of interests to declare for Jian Hu, Qinzi Xu, Charles McTiernan, Yen-Chun Lai, and David Osei-Hwedieh. Mark Gladwin receives National Institutes of Health (NIH) grant funding, and is a consultant for Bayer for sickle cell disease. He is also the co-inventor of an NIH patent for the use of nitrite for cardiovascular indications. He also receives royalties as co-author of a textbook of medical students.

No financial assistance was received for preparing this manuscript.

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Authors and Affiliations

  1. Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, E1226 BST 200 Lothrop Street, Pittsburgh, PA, 15213, USA

    Jian Hu, Qinzi Xu, Charles McTiernan, Yen-Chun Lai, David Osei-Hwedieh & Mark Gladwin

  2. Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, USA

    Mark Gladwin

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  1. Jian Hu
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  2. Qinzi Xu
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Correspondence to Jian Hu.

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Hu, J., Xu, Q., McTiernan, C. et al. Novel Targets of Drug Treatment for Pulmonary Hypertension. Am J Cardiovasc Drugs 15, 225–234 (2015). https://doi.org/10.1007/s40256-015-0125-4

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