The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Disruption of PPARγ/β-catenin–mediated regulation of apelin impairs BMP-induced mouse and human pulmonary arterial EC survival
Open accessAbstract
Reduced bone morphogenetic protein receptor 2 (BMPR2) expression in patients with pulmonary arterial hypertension (PAH) can impair pulmonary arterial EC (PAEC) function. This can adversely affect EC survival and promote SMC proliferation. We hypothesized that interventions to normalize expression of genes that are targets of BMPR2 signaling could restore PAEC function and prevent or reverse PAH. Here we have characterized, in human PAECs, a BMPR2-mediated transcriptional complex between PPARγ and β-catenin and shown that disruption of this complex impaired BMP-mediated PAEC survival. Using whole genome-wide ChIP-Chip promoter analysis and gene expression microarrays, we delineated PPARγ/β-catenin-dependent transcription of target genes including APLN, which encodes apelin. We documented reduced PAEC expression of apelin in PAH patients versus controls. In cell culture experiments, we showed that apelin-deficient PAECs were prone to apoptosis and promoted pulmonary arterial SMC (PASMC) proliferation. Conversely, we established that apelin, like BMPR2 ligands, suppressed proliferation and induced apoptosis of PASMCs. Consistent with these functions, administration of apelin reversed PAH in mice with reduced production of apelin resulting from deletion of PPARγ in ECs. Taken together, our findings suggest that apelin could be effective in treating PAH by rescuing BMPR2 and PAEC dysfunction.
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Cites
Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes
Nissen, S. E., & Wolski, K. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa072761 · Cited by 4,675
Leesnitzer, L. M., Parks, D. J., Bledsoe, R. K., Cobb, J. E., Collins, J. L., Consler, T. G., Davis, R. G., Hull-Ryde, E. A., Lenhard, J. M., Patel, L., et al. (2002) · Biochemistry · doi:10.1021/bi0159581 · Cited by 566
Fatty Acid Transduction of Nitric Oxide Signaling
Baker, P. R. S., Lin, Y., Schopfer, F. J., Woodcock, S. R., Groeger, A. L., Batthyany, C., Sweeney, S., Long, M. H., Iles, K. E., Baker, L. M. S., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504212200 · Cited by 358
Self-citationNitro-fatty acid formation and signaling
Freeman, B. A., Baker, P. R. S., Schopfer, F. J., Woodcock, S. R., Napolitano, A., & d'Ischia, M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.r800004200 · Cited by 265
Self-citationCovalent Peroxisome Proliferator-activated Receptor γ Adduction by Nitro-fatty Acids
Schopfer, F. J., Cole, M. P., Groeger, A. L., Chen, C.-S., Khoo, N. K. H., Woodcock, S. R., Golin-Bisello, F., Motanya, U. N., Li, Y., Zhang, J., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.091512 · Cited by 171
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Inflammation and immunity in the pathogenesis of pulmonary arterial hypertension
Rabinovitch, M., Guignabert, C., Humbert, M., & Nicolls, M. R. (2014) · Circulation Research · doi:10.1161/circresaha.113.301141 · Cited by 1,029
Self-citationKim, J., Kang, Y., Kojima, Y., Lighthouse, J. K., Hu, X., Aldred, M. A., McLean, D. L., Park, H., Comhair, S. A., Greif, D. M., et al. (2013) · Nature Medicine · doi:10.1038/nm.3040 · Cited by 356
Advances in Therapeutic Interventions for Patients With Pulmonary Arterial Hypertension
Humbert, M., Lau, E. M. T., Montani, D., Jaïs, X., Sitbon, O., & Simonneau, G. (2014) · Circulation · doi:10.1161/circulationaha.114.006974 · Cited by 342
Endothelial cells in the pathogenesis of pulmonary arterial hypertension
Evans, C. E., Cober, N. D., Dai, Z., Stewart, D. J., & Zhao, Y.-Y. (2021) · European Respiratory Journal · doi:10.1183/13993003.03957-2020 · Cited by 325
The Metabolic Theory of Pulmonary Arterial Hypertension
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Metadata
- Authors
- Alastalo, T.-P., Li, M., de Jesus Perez, V., Pham, D., Sawada, H., Wang, J. K., Koskenvuo, M., Wang, L., Freeman, B. A., Chang, H. Y., & Rabinovitch, M.
- Venue
- Journal of Clinical Investigation
- Published
- 2011-09-01
- Volume
- 121
- Issue
- 9
- Pages
- 3735-3746
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2157122261
- Cited by
- 254
- References
- 5
- FWCI
- 12.94
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Alastalo, T.-P., Li, M., de Jesus Perez, V., Pham, D., Sawada, H., Wang, J. K., Koskenvuo, M., Wang, L., Freeman, B. A., Chang, H. Y., & Rabinovitch, M. (2011). Disruption of PPARγ/β-catenin–mediated regulation of apelin impairs BMP-induced mouse and human pulmonary arterial EC survival. Journal of Clinical Investigation. https://doi.org/10.1172/jci43382
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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