Kinases as potential targets for treatment of pulmonary hypertension and right ventricular dysfunction.

Autor: Weiss A; Department of Internal Medicine, Justus-Liebig University Giessen, Giessen, Germany.; German Center for Lung Research (DZL), Giessen, Germany., Boehm M; Department of Internal Medicine, Justus-Liebig University Giessen, Giessen, Germany.; German Center for Lung Research (DZL), Giessen, Germany., Egemnazarov B; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria., Grimminger F; Department of Internal Medicine, Justus-Liebig University Giessen, Giessen, Germany.; German Center for Lung Research (DZL), Giessen, Germany., Savai Pullamsetti S; Department IV, Max-Planck Institute for Heart and Lung Research, Bad Nauheim, Germany., Kwapiszewska G; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.; Otto Loewi Center, Physiology, Medical University of Graz, Graz, Austria., Schermuly RT; Department of Internal Medicine, Justus-Liebig University Giessen, Giessen, Germany.
Jazyk: angličtina
Zdroj: British journal of pharmacology [Br J Pharmacol] 2021 Jan; Vol. 178 (1), pp. 31-53. Date of Electronic Publication: 2020 Feb 04.
DOI: 10.1111/bph.14919
Abstrakt: Pulmonary hypertension (PH) is a progressive pulmonary vasculopathy that causes chronic right ventricular pressure overload and often leads to right ventricular failure. Various kinase inhibitors have been studied in the setting of PH and either improved or worsened the disease, highlighting the importance of understanding the specific role of the respective kinases in a spatiotemporal cellular context. In this review, we will summarize the knowledge on the role of kinases in PH and focus on druggable targets for which certain criteria are met: (a) deregulation of the kinase in PH; (b) small-molecule inhibitors are available (e.g. from the oncology field); (c) preclinical studies have shown their efficacy in PH models; and (d) when available, therapeutic exploitation in human PH has been initiated. Along this line, clinical considerations such as personalized medicine approaches to predict therapy response and adverse side events such as cardiotoxicity together with their clinical management are discussed. LINKED ARTICLES: This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc.
(© 2019 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)
Databáze: MEDLINE
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