Abstract | BACKGROUND:
Pulmonary veno-occlusive disease is caused by excessive cell proliferation and fibrosis, which obliterate the lumen of pulmonary venules, leading to pulmonary hypertension, right ventricular failure, and death. This condition has no effective treatment and a 5-year survival of <5%. Understanding the mechanism of this disease and designing effective therapies are urgently needed. METHODS AND RESULTS: CONCLUSIONS: Our results suggest that ERG and APLNR are essential for endothelial homeostasis in venules in the lung and that perturbation in ERG- APLNR signaling is crucial for the development of pulmonary veno-occlusive disease. We identify this pathway as a potential therapeutic target for the treatment of this incurable disease.
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Authors | Christopher Lathen, Yu Zhang, Jennifer Chow, Martanday Singh, Grace Lin, Vishal Nigam, Yasser A Ashraf, Jason X Yuan, Ivan M Robbins, Patricia A Thistlethwaite |
Journal | Circulation
(Circulation)
Vol. 130
Issue 14
Pg. 1179-91
(Sep 30 2014)
ISSN: 1524-4539 [Electronic] United States |
PMID | 25062690
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | © 2014 American Heart Association, Inc. |
Chemical References |
- APLNR protein, human
- Apelin Receptors
- Aplnr protein, mouse
- ERG protein, human
- ERG protein, mouse
- Oncogene Proteins
- Receptors, G-Protein-Coupled
- Trans-Activators
- Transcription Factors
- Transcriptional Regulator ERG
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Topics |
- Animals
- Apelin Receptors
- Cell Proliferation
- Cells, Cultured
- Endothelial Cells
(pathology)
- Female
- Gene Expression
(physiology)
- Humans
- Lac Operon
- Lung Transplantation
- Male
- Mice
- Mice, Knockout
- Oncogene Proteins
(genetics, metabolism)
- Phenotype
- Promoter Regions, Genetic
(physiology)
- Pulmonary Artery
(pathology)
- Pulmonary Veins
(pathology)
- Pulmonary Veno-Occlusive Disease
(pathology, surgery)
- Receptors, G-Protein-Coupled
(genetics, metabolism)
- Signal Transduction
(physiology)
- Trans-Activators
(genetics, metabolism)
- Transcription Factors
(genetics, metabolism)
- Transcriptional Regulator ERG
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