The Role of Bone Morphogenetic Protein Receptor Type 2 (<i>BMPR2</i>) and the Prospects of Utilizing Induced Pluripotent Stem Cells (iPSCs) in Pulmonary Arterial Hypertension Disease Modeling
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by increased pulmonary vascular resistance (PVR), causing right ventricular hypertrophy and ultimately death from right heart failure. Heterozygous mutations in the bone morphogenetic protein receptor type 2 (<i>BMPR2...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/23/3823 |
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| author | Anichavezhi Devendran Sumanta Kar Rasheed Bailey Maria Giovanna Trivieri |
| author_facet | Anichavezhi Devendran Sumanta Kar Rasheed Bailey Maria Giovanna Trivieri |
| author_sort | Anichavezhi Devendran |
| collection | DOAJ |
| description | Pulmonary arterial hypertension (PAH) is a progressive disease characterized by increased pulmonary vascular resistance (PVR), causing right ventricular hypertrophy and ultimately death from right heart failure. Heterozygous mutations in the bone morphogenetic protein receptor type 2 (<i>BMPR2</i>) are linked to approximately 80% of hereditary, and 20% of idiopathic PAH cases, respectively. While patients carrying a <i>BMPR2</i> gene mutation are more prone to develop PAH than non-carriers, only 20% will develop the disease, whereas the majority will remain asymptomatic. PAH is characterized by extreme vascular remodeling that causes pulmonary arterial endothelial cell (PAEC) dysfunction, impaired apoptosis, and uncontrolled proliferation of the pulmonary arterial smooth muscle cells (PASMCs). To date, progress in understanding the pathophysiology of PAH has been hampered by limited access to human tissue samples and inadequacy of animal models to accurately mimic the pathogenesis of human disease. Along with the advent of induced pluripotent stem cell (iPSC) technology, there has been an increasing interest in using this tool to develop patient-specific cellular models that precisely replicate the pathogenesis of PAH. In this review, we summarize the currently available approaches in iPSC-based PAH disease modeling and explore how this technology could be harnessed for drug discovery and to widen our understanding of the pathophysiology of PAH. |
| first_indexed | 2024-03-09T17:51:21Z |
| format | Article |
| id | doaj.art-62d31704a3014665940d64b4d3d409a0 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T17:51:21Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-62d31704a3014665940d64b4d3d409a02023-11-24T10:44:22ZengMDPI AGCells2073-44092022-11-011123382310.3390/cells11233823The Role of Bone Morphogenetic Protein Receptor Type 2 (<i>BMPR2</i>) and the Prospects of Utilizing Induced Pluripotent Stem Cells (iPSCs) in Pulmonary Arterial Hypertension Disease ModelingAnichavezhi Devendran0Sumanta Kar1Rasheed Bailey2Maria Giovanna Trivieri3Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USACardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USACardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USACardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USAPulmonary arterial hypertension (PAH) is a progressive disease characterized by increased pulmonary vascular resistance (PVR), causing right ventricular hypertrophy and ultimately death from right heart failure. Heterozygous mutations in the bone morphogenetic protein receptor type 2 (<i>BMPR2</i>) are linked to approximately 80% of hereditary, and 20% of idiopathic PAH cases, respectively. While patients carrying a <i>BMPR2</i> gene mutation are more prone to develop PAH than non-carriers, only 20% will develop the disease, whereas the majority will remain asymptomatic. PAH is characterized by extreme vascular remodeling that causes pulmonary arterial endothelial cell (PAEC) dysfunction, impaired apoptosis, and uncontrolled proliferation of the pulmonary arterial smooth muscle cells (PASMCs). To date, progress in understanding the pathophysiology of PAH has been hampered by limited access to human tissue samples and inadequacy of animal models to accurately mimic the pathogenesis of human disease. Along with the advent of induced pluripotent stem cell (iPSC) technology, there has been an increasing interest in using this tool to develop patient-specific cellular models that precisely replicate the pathogenesis of PAH. In this review, we summarize the currently available approaches in iPSC-based PAH disease modeling and explore how this technology could be harnessed for drug discovery and to widen our understanding of the pathophysiology of PAH.https://www.mdpi.com/2073-4409/11/23/3823pulmonary arterial hypertensionpulmonary vascular resistancevascular remodelinginduced pluripotent stem celldisease modelingpulmonary arterial endothelial cells |
| spellingShingle | Anichavezhi Devendran Sumanta Kar Rasheed Bailey Maria Giovanna Trivieri The Role of Bone Morphogenetic Protein Receptor Type 2 (<i>BMPR2</i>) and the Prospects of Utilizing Induced Pluripotent Stem Cells (iPSCs) in Pulmonary Arterial Hypertension Disease Modeling Cells pulmonary arterial hypertension pulmonary vascular resistance vascular remodeling induced pluripotent stem cell disease modeling pulmonary arterial endothelial cells |
| title | The Role of Bone Morphogenetic Protein Receptor Type 2 (<i>BMPR2</i>) and the Prospects of Utilizing Induced Pluripotent Stem Cells (iPSCs) in Pulmonary Arterial Hypertension Disease Modeling |
| title_full | The Role of Bone Morphogenetic Protein Receptor Type 2 (<i>BMPR2</i>) and the Prospects of Utilizing Induced Pluripotent Stem Cells (iPSCs) in Pulmonary Arterial Hypertension Disease Modeling |
| title_fullStr | The Role of Bone Morphogenetic Protein Receptor Type 2 (<i>BMPR2</i>) and the Prospects of Utilizing Induced Pluripotent Stem Cells (iPSCs) in Pulmonary Arterial Hypertension Disease Modeling |
| title_full_unstemmed | The Role of Bone Morphogenetic Protein Receptor Type 2 (<i>BMPR2</i>) and the Prospects of Utilizing Induced Pluripotent Stem Cells (iPSCs) in Pulmonary Arterial Hypertension Disease Modeling |
| title_short | The Role of Bone Morphogenetic Protein Receptor Type 2 (<i>BMPR2</i>) and the Prospects of Utilizing Induced Pluripotent Stem Cells (iPSCs) in Pulmonary Arterial Hypertension Disease Modeling |
| title_sort | role of bone morphogenetic protein receptor type 2 i bmpr2 i and the prospects of utilizing induced pluripotent stem cells ipscs in pulmonary arterial hypertension disease modeling |
| topic | pulmonary arterial hypertension pulmonary vascular resistance vascular remodeling induced pluripotent stem cell disease modeling pulmonary arterial endothelial cells |
| url | https://www.mdpi.com/2073-4409/11/23/3823 |
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