Expression of angiogenesis-related molecules in plexiform lesions in severe pulmonary hypertension: Evidence for a process of disordered angiogenesis

Rubin M. Tuder, Mati Chacon, Lori Alger, Jun Wang, Laimute Taraseviciene-Stewart, Yasunori Kasahara, Carlyne D. Cool, Anne E. Bishop, Mark Geraci, Gregg L. Semenza, Magdi Yacoub, Julia M. Polak, Norbert F. Voelkel

Research output: Contribution to journalArticle

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 H1F-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 P13 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.

Original languageEnglish (US)
Pages (from-to)367-374
Number of pages8
JournalJournal of Pathology
Volume195
Issue number3
DOIs
StatePublished - Nov 7 2001

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Keywords

  • Angiogenesis
  • Endothelial cells
  • Plexiform lesion
  • Pulmonary hypertension
  • VEGF
  • VEGFR-2

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

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. (2001). Expression of angiogenesis-related molecules in plexiform lesions in severe pulmonary hypertension: Evidence for a process of disordered angiogenesis. Journal of Pathology, 195(3), 367-374. https://doi.org/10.1002/path.953