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

330 Citations (Scopus)

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 - 2001
Externally publishedYes

Fingerprint

Pulmonary Hypertension
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor
Lung
Endothelial Cells
Hypoxia-Inducible Factor 1
Collagen Diseases
Vascular Endothelial Growth Factor Receptor-2
Messenger RNA
Proteins
src-Family Kinases
Congenital Heart Defects
Vascular Diseases
Pulmonary Artery
In Situ Hybridization
Signal Transduction
Transcription Factors
Phosphotransferases
Immunohistochemistry

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., ... 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

Expression of angiogenesis-related molecules in plexiform lesions in severe pulmonary hypertension : Evidence for a process of disordered angiogenesis. / Tuder, Rubin M.; Chacon, Mati; Alger, Lori; Wang, Jun; Taraseviciene-Stewart, Laimute; Kasahara, Yasunori; Cool, Carlyne D.; Bishop, Anne E.; Geraci, Mark; Semenza, Gregg L.; Yacoub, Magdi; Polak, Julia M.; Voelkel, Norbert F.

In: Journal of Pathology, Vol. 195, No. 3, 2001, p. 367-374.

Research output: Contribution to journalArticle

Tuder, RM, Chacon, M, Alger, L, Wang, J, Taraseviciene-Stewart, L, Kasahara, Y, Cool, CD, Bishop, AE, Geraci, M, Semenza, GL, Yacoub, M, Polak, JM & Voelkel, NF 2001, 'Expression of angiogenesis-related molecules in plexiform lesions in severe pulmonary hypertension: Evidence for a process of disordered angiogenesis', Journal of Pathology, vol. 195, no. 3, pp. 367-374. https://doi.org/10.1002/path.953
Tuder, Rubin M. ; Chacon, Mati ; Alger, Lori ; Wang, Jun ; Taraseviciene-Stewart, Laimute ; Kasahara, Yasunori ; Cool, Carlyne D. ; Bishop, Anne E. ; Geraci, Mark ; Semenza, Gregg L. ; Yacoub, Magdi ; Polak, Julia M. ; Voelkel, Norbert F. / Expression of angiogenesis-related molecules in plexiform lesions in severe pulmonary hypertension : Evidence for a process of disordered angiogenesis. In: Journal of Pathology. 2001 ; Vol. 195, No. 3. pp. 367-374.
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