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Expression of angiogenesis‐related molecules in plexiform lesions in severe pulmonary hypertension: evidence for a process of disordered angiogenesis
Abstract
Pulmonary arteries of patients with severe pulmonary hypertension (SPH) presenting in an idiopathic form (primary PH‐PPH) or associated with congenital heart malformations or collagen vascular diseases show plexiform lesions. It is postulated that in lungs with SPH, endothelial cells in plexiform lesions express genes encoding for proteins involved in angiogenesis, in particular, vascular endothelial growth factor (VEGF) and those involved in VEGF receptor‐2 (VEGFR‐2) signalling. On immunohistochemistry and in situ hybridization, endothelial cells in the plexiform lesions expressed VEGF mRNA and protein and overexpressed the mRNA and protein of VEGFR‐2, and the transcription factor subunits HIF‐1α and HIF‐1β of hypoxia inducible factor, which are responsible for the hypoxia‐dependent induction of VEGF. When compared with normal lungs, SPH lungs showed decreased expression of the kinases PI3 kinase and src, which, together with Akt, relay the signal transduction downstream of VEGFR‐2. Because markers of angiogenesis are expressed in plexiform lesions in SPH, it is proposed that these lesions may form by a process of disordered angiogenesis. Copyright © 2001 John Wiley & Sons, Ltd.
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Metadata
- Authors
- Tuder, R. M., Chacon, M., Alger, L., Wang, J., Taraseviciene‐Stewart, L., Kasahara, Y., Cool, C. D., Bishop, A. E., Geraci, M., Semenza, G. L., Yacoub, M., Polak, J. M., & Voelkel, N. F.
- Venue
- The Journal of Pathology
- Publisher
- Wiley
- Published
- 2001-08-29
- Volume
- 195
- Issue
- 3
- Pages
- 367-374
- ISSN
- 0022-3417 (ISSN-L)
- 1096-9896
- OpenAlex
- W2043826113
- Cited by
- 500
- References
- 4
- FWCI
- 10.20
- Type
- journal article
- Language
- en
- Open access
- closed
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