Novel Advances in Modifying BMPR2 Signaling in PAH
1
Division Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Stanford University, Stanford, CA 94305, USA
2
Vera Moulton Wall Center for Pulmonary Vascular Diseases, Stanford, CA 94305, USA
3
Institute for Experimental and Clinical Pharmacology and Toxicology, Albert-Ludwigs University Freiburg, 79104 Freiburg, Germany
*
Author to whom correspondence should be addressed.
Genes 2021, 12(1), 8; https://doi.org/10.3390/genes12010008
Received: 30 November 2020
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Revised: 19 December 2020
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Accepted: 21 December 2020
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Published: 23 December 2020
(This article belongs to the Special Issue Genetics and Genomics of Pulmonary Arterial Hypertension)
Pulmonary Arterial Hypertension (PAH) is a disease of the pulmonary arteries, that is characterized by progressive narrowing of the pulmonary arterial lumen and increased pulmonary vascular resistance, ultimately leading to right ventricular dysfunction, heart failure and premature death. Current treatments mainly target pulmonary vasodilation and leave the progressive vascular remodeling unchecked resulting in persistent high morbidity and mortality in PAH even with treatment. Therefore, novel therapeutic strategies are urgently needed. Loss of function mutations of the Bone Morphogenetic Protein Receptor 2 (BMPR2) are the most common genetic factor in hereditary forms of PAH, suggesting that the BMPR2 pathway is fundamentally important in the pathogenesis. Dysfunctional BMPR2 signaling recapitulates the cellular abnormalities in PAH as well as the pathobiology in experimental pulmonary hypertension (PH). Approaches to restore BMPR2 signaling by increasing the expression of BMPR2 or its downstream signaling targets are currently actively explored as novel ways to prevent and improve experimental PH as well as PAH in patients. Here, we summarize existing as well as novel potential treatment strategies for PAH that activate the BMPR2 receptor pharmaceutically or genetically, increase the receptor availability at the cell surface, or reconstitute downstream BMPR2 signaling.
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Keywords:
PAH; pulmonary hypertension; bone morphogenetic protein receptor 2; signaling; repurposed drugs; pharmaceuticals; miRNA; clinical trials
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
MDPI and ACS Style
Dannewitz Prosseda, S.; Ali, M.K.; Spiekerkoetter, E. Novel Advances in Modifying BMPR2 Signaling in PAH. Genes 2021, 12, 8. https://doi.org/10.3390/genes12010008
AMA Style
Dannewitz Prosseda S, Ali MK, Spiekerkoetter E. Novel Advances in Modifying BMPR2 Signaling in PAH. Genes. 2021; 12(1):8. https://doi.org/10.3390/genes12010008
Chicago/Turabian StyleDannewitz Prosseda, Svenja, Md K. Ali, and Edda Spiekerkoetter. 2021. "Novel Advances in Modifying BMPR2 Signaling in PAH" Genes 12, no. 1: 8. https://doi.org/10.3390/genes12010008
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