Novel Pharmacological Targets for Pulmonary Arterial Hypertension


Posted: 2021-09-24 19:00:00
Compr Physiol . 2021 Sep 23;11(4):1-53. doi: 10.1002/cphy.c200015. Affiliations Expand Affiliation 1 Division of Pulmonary, Sleep and Critical Care Medicine, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island, USA. Item in Clipboard James R Klinger. Compr Physiol. 2021. Show details Display options Display options Format Compr Physiol . 2021 Sep 23;11(4):1-53. doi: 10.1002/cphy.c200015. Affiliation 1 Division of Pulmonary, Sleep and Critical Care Medicine, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island, USA. Item in Clipboard CiteDisplay options Display options Format Abstract Pulmonary arterial hypertension (PAH) is a rare disease characterized by an obliterative vasculopathy of the distal pulmonary circulation that results in severe elevation in pulmonary pressure and pulmonary vascular resistance. PAH is a progressive and devastating disease that usually results in right heart failure and death. Currently available medications have only moderate effects and none are curative. Thus, there is a pressing need for new pharmacologic approaches to this disease. In order to meaningfully advance the treatment of PAH, new agents must target the underlying cause of disease induction and progression. This review discusses the extensive work that has been done in the areas of altered glucose metabolism, tyrosine kinase inhibitions, signaling pathways associated with disease causing gene mutations such as the bone morphogenic protein receptor 2, and inflammation and immunomodulation including the effects of mesenchymal stem cells and the extracellular vesicles they secrete. Epigenetic modifications including the roles of micro RNAs, DNA methylation, histone acetylation and transcription factors that modulate pulmonary vascular remodeling are also reviewed. A brief background of each area of interest is provided with emphasis on those components that have potential to be exploited for the treatment of PAH. Significant findings of cell-based and animal studies and, where available, the results of early clinical trials, are presented to illustrate the potential of these novel therapeutic targets. Current challenges to the development of small peptides and biologicals for the treatment of PAH and direction for future studies are also briefly discussed. © 2021 American Physiological Society. Compr Physiol 11:1-53, 2021. Copyright © 2021 American Physiological Society. All rights reserved. References Adir Y, Humbert M. Pulmonary hypertension in patients with chronic myeloproliferative disorders. Eur Respir J 35 (6): 1396-1406, 2010. DOI: 10.1183/09031936.00175909. Aiello RJ, Bourassa PA, Zhang Q, Dubins J, Goldberg DR, De Lombaert S, Humbert M, Guignabert C, Cavasin MA, McKinsey TA, Paralkar V. Tryptophan hydroxylase 1 inhibition impacts pulmonary vascular remodeling in two rat models of pulmonary hypertension. J Pharmacol Exp Ther 360 (2): 267-279, 2017. DOI: 10.1124/jpet.116.237933. Akagi S, Nakamura K, Matsubara H, Kondo M, Miura D, Matoba T, Egashira K, Ito H. Intratracheal administration of prostacyclin analogue-incorporated nanoparticles ameliorates the development of monocrotaline and sugen-hypoxia-induced pulmonary arterial hypertension. J Cardiovasc Pharmacol 67 (4): 290-298, 2016. DOI: 10.1097/FJC.0000000000000352. Akiyama K, Chen C, Wang D, Xu X, Qu C, Yamaza T, Cai T, Chen W, Sun L, Shi S. Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis. Cell Stem Cell 10 (5): 544-555, 2012. DOI: 10.1016/j.stem.2012.03.007. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular Biology of the Cell. New York, NY: Garland Science, 2002. ISBN: 0-8153-3218-1. Show all 548 references [x] Cite Copy Format: Send To [x]

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バイオクイックニュース日本語版:エクソソーム特集

バイオクイックニュース日本語版
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