Genetic variants of the BMPR2 gene and their contribution to the development of pulmonary arterial hypertension.
1 Faculty of Medicine and Nutrition UJED Av. Universidad zona centro and Fanny Anitúa s/n. C.P. 34000. Durango, Dgo., Mexico.
2 Department of genetics, Juárez University of the State of Durango., Durango, Dgo. México.
Review Article
GSC Advanced Research and Reviews, 2024, 19(03), 311–318.
Article DOI: 10.30574/gscarr.2024.19.3.0227
Publication history:
Received on 17 May 2024; revised on 24 June 2024; accepted on 26 June 2024
Abstract:
Pulmonary arterial hypertension (PAH) is a devastating disease characterized by a progressive increase in pressure in the pulmonary arteries. This leads to vascular remodeling and, eventually, right heart failure. Variants in the BMPR2 gene, which encodes the bone morphogenetic protein receptor type 2, are the most common genetic cause of hereditary and idiopathic PAH. These variants disrupt the transforming growth factor-beta (TGF-β) signaling pathway, triggering abnormal proliferation of pulmonary artery smooth muscle cells and apoptosis of endothelial cells. This results in complex vascular remodeling, characterized by thickening of the vascular walls, formation of plexiform lesions, and in situ thrombosis. Endothelial dysfunction also contributes to an imbalance between vasoconstrictors and vasodilators, exacerbating pulmonary hypertension. While current therapies aim to restore this balance, they have a limited impact on the underlying vascular remodeling.
Emerging strategies seek to restore the functionality of BMPR2 variants or enhance their signaling through agonists and read-through molecules. Additionally, a higher penetrance of the disease has been observed in women carrying BMPR2 variants, suggesting an interaction with sex hormone metabolism.
The research aims to understand the role of BMPR2 gene variants in the development of PAH and to explore emerging strategies to restore the functionality of these variants or enhance their signaling.
Keywords:
BMPR2 gene; Genetic variants; Pulmonary arterial hypertension; Pulmonary vascular remodeling.
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Copyright © 2024 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0
