The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
Signaling Molecules in Nonfamilial Pulmonary Hypertension
Open accessAbstract
BACKGROUND: Biochemical, genetic, and clinical evidence indicates that smooth-muscle proliferation around small pulmonary vessels is an essential part of the pathogenesis of pulmonary hypertension. Mutations in the bone morphogenetic protein receptor type 2 (BMPR2) have been linked to familial cases of pulmonary hypertension, but the molecular basis of the common nonfamilial forms is unknown. METHODS: We evaluated the pattern of expression of angiopoietin-1, a protein involved in the recruitment of smooth-muscle cells around blood vessels; TIE2, the endothelial-specific receptor for angiopoietin-1; and bone morphogenetic protein receptor type 1A (BMPR1A) and BMPR2 in lung-biopsy specimens from patients with pulmonary hypertension and from normotensive control patients. The effect of angiopoietin-1 on the modulation of BMPR expression was also evaluated in subcultures of human pulmonary arteriolar endothelial cells. RESULTS: The expression of angiopoietin-1 messenger RNA and the protein itself and the phosphorylation of TIE2 were strongly up-regulated in the lungs of patients with various forms of pulmonary hypertension, correlating directly with the severity of disease. A mechanistic link between familial and acquired pulmonary hypertension was demonstrated by the finding that angiopoietin-1 shuts off the expression of BMPR1A, a transmembrane protein required for BMPR2 signaling, in pulmonary arteriolar endothelial cells. Similarly, we found that the expression of BMPR1A was severely reduced in the lungs of patients with various forms of acquired as well as primary nonfamilial pulmonary hypertension. CONCLUSIONS: These findings suggest that all forms of pulmonary hypertension are linked by defects in the signaling pathway involving angiopoietin-1, TIE2, BMPR1A, and BMPR2 and consequently identify specific molecular targets for therapeutic intervention.
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Cites
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Self-citationPulmonary endarterectomy: experience and lessons learned in 1,500 cases
Jamieson, S. W., Kapelanski, D. P., Sakakibara, N., Manecke, G. R., Thistlethwaite, P. A., Kerr, K. M., Channick, R. N., Fedullo, P. F., & Auger, W. R. (2003) · The Annals of Thoracic Surgery · doi:10.1016/s0003-4975(03)00828-2 · Cited by 770
Self-citationEndothelial Dysfunction in Pulmonary Hypertension
Budhiraja, R., Tuder, R. M., & Hassoun, P. M. (2004) · Circulation · doi:10.1161/01.cir.0000102381.57477.50 · Cited by 768
Pathologic assessment of vasculopathies in pulmonary hypertension
Pietra, G. G., Capron, F., Stewart, S., Leone, O., Humbert, M., Robbins, I. M., Reid, L. M., & Tuder, R. M. (2004) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2004.02.033 · Cited by 709
Diastolic Pulmonary Vascular Pressure Gradient
Gerges, C., Gerges, M., Lang, M. B., Zhang, Y., Jakowitsch, J., Probst, P., Maurer, G., & Lang, I. M. (2013) · Chest · doi:10.1378/chest.12-1653 · Cited by 368
Metadata
- Authors
- Du, L., Sullivan, C. C., Chu, D., Cho, A. J., Kido, M., Wolf, P. L., Yuan, J. X.-J., Deutsch, R., Jamieson, S. W., & Thistlethwaite, P. A.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2003-02-06
- Volume
- 348
- Issue
- 6
- Pages
- 500-509
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2050384089
- Cited by
- 400
- References
- 24
- FWCI
- 30.79
- Type
- journal article
- Language
- en
- Open access
- bronze
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