Genes in pediatric pulmonary arterial hypertension and the most promising BMPR2 gene therapy

Pulmonary arterial hypertension (PAH) is a rare but progressive and lethal vascular disease of diverse etiologies, mainly caused by proliferation of endothelial cells, smooth muscle cells in the pulmonary artery, and fibroblasts, which ultimately leads to right-heart hypertrophy and cardiac failure....

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Main Authors: Lingling Dai, Lizhong Du
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-11-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2022.961848/full
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author Lingling Dai
Lizhong Du
author_facet Lingling Dai
Lizhong Du
author_sort Lingling Dai
collection DOAJ
description Pulmonary arterial hypertension (PAH) is a rare but progressive and lethal vascular disease of diverse etiologies, mainly caused by proliferation of endothelial cells, smooth muscle cells in the pulmonary artery, and fibroblasts, which ultimately leads to right-heart hypertrophy and cardiac failure. Recent genetic studies of childhood-onset PAH report that there is a greater genetic burden in children than in adults. Since the first-identified pathogenic gene of PAH, BMPR2, which encodes bone morphogenetic protein receptor 2, a receptor in the transforming growth factor-β superfamily, was discovered, novel causal genes have been identified and substantially sharpened our insights into the molecular genetics of childhood-onset PAH. Currently, some newly identified deleterious genetic variants in additional genes implicated in childhood-onset PAH, such as potassium channels (KCNK3) and transcription factors (TBX4 and SOX17), have been reported and have greatly updated our understanding of the disease mechanism. In this review, we summarized and discussed the advances of genetic variants underlying childhood-onset PAH susceptibility and potential mechanism, and the most promising BMPR2 gene therapy and gene delivery approaches to treat childhood-onset PAH in the future.
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spelling doaj.art-4dd4480db5714e95bef7048284755c8e2022-12-22T02:53:38ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-11-011310.3389/fgene.2022.961848961848Genes in pediatric pulmonary arterial hypertension and the most promising BMPR2 gene therapyLingling DaiLizhong DuPulmonary arterial hypertension (PAH) is a rare but progressive and lethal vascular disease of diverse etiologies, mainly caused by proliferation of endothelial cells, smooth muscle cells in the pulmonary artery, and fibroblasts, which ultimately leads to right-heart hypertrophy and cardiac failure. Recent genetic studies of childhood-onset PAH report that there is a greater genetic burden in children than in adults. Since the first-identified pathogenic gene of PAH, BMPR2, which encodes bone morphogenetic protein receptor 2, a receptor in the transforming growth factor-β superfamily, was discovered, novel causal genes have been identified and substantially sharpened our insights into the molecular genetics of childhood-onset PAH. Currently, some newly identified deleterious genetic variants in additional genes implicated in childhood-onset PAH, such as potassium channels (KCNK3) and transcription factors (TBX4 and SOX17), have been reported and have greatly updated our understanding of the disease mechanism. In this review, we summarized and discussed the advances of genetic variants underlying childhood-onset PAH susceptibility and potential mechanism, and the most promising BMPR2 gene therapy and gene delivery approaches to treat childhood-onset PAH in the future.https://www.frontiersin.org/articles/10.3389/fgene.2022.961848/fullgeneticsgene therapyPAHBMPR2childhood-onset
spellingShingle Lingling Dai
Lizhong Du
Genes in pediatric pulmonary arterial hypertension and the most promising BMPR2 gene therapy
Frontiers in Genetics
genetics
gene therapy
PAH
BMPR2
childhood-onset
title Genes in pediatric pulmonary arterial hypertension and the most promising BMPR2 gene therapy
title_full Genes in pediatric pulmonary arterial hypertension and the most promising BMPR2 gene therapy
title_fullStr Genes in pediatric pulmonary arterial hypertension and the most promising BMPR2 gene therapy
title_full_unstemmed Genes in pediatric pulmonary arterial hypertension and the most promising BMPR2 gene therapy
title_short Genes in pediatric pulmonary arterial hypertension and the most promising BMPR2 gene therapy
title_sort genes in pediatric pulmonary arterial hypertension and the most promising bmpr2 gene therapy
topic genetics
gene therapy
PAH
BMPR2
childhood-onset
url https://www.frontiersin.org/articles/10.3389/fgene.2022.961848/full
work_keys_str_mv AT linglingdai genesinpediatricpulmonaryarterialhypertensionandthemostpromisingbmpr2genetherapy
AT lizhongdu genesinpediatricpulmonaryarterialhypertensionandthemostpromisingbmpr2genetherapy