Pulmonary vein stenosis: Expression of receptor tyrosine kinases by lesional cells

Wolfram F J Riedlinger, Amy L. Juraszek, Kathy J. Jenkins, Alan W. Nugent, Sowmya Balasubramanian, Monica L. Calicchio, Mark W. Kieran, Tucker Collins

Research output: Contribution to journalArticle

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Abstract

Background: Primary pulmonary vein stenosis (PVS) is a progressive disorder of infants. Although catheter based intervention and chemotherapy are used to manage the disorder, the benefit of these approaches is reduced considerably by restenosis. The nature of the intimal cells causing the occlusive lesions in PVS is poorly understood. Methods: Seven PVS cases were studied with antibodies for smooth muscle actin (SMA), muscle-specific actin (MSA), monoclonal desmin, S100 protein, CD31, CD34, CD45RO, CD68, CD99, Ki-67 (MIB-I), and with antibodies directed against several receptor tyrosine kinases (RTK), including platelet-derived growth factor alpha and beta receptor (PDGFR-α and -β), epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR), vascular endothelial growth factor 1 and 2 receptor (VEGFR), and stem cell factor receptor (c-kit). Results: Lesional cells stained strongly and diffusely with SMA and MSA, but not for macrophage, lymphocyte, endothelial markers, or for Ki-67. RTK expression was strong and diffuse for PDGFR-α and -β, FGFR, and VEGFR-2. Lesional cells stained for VEGF and PDGF β receptor was phosphorylated. Conclusions: The histologic appearance, and the strong diffuse immunoreactivity for smooth muscle markers, indicates that the intimal lesional cells are myofibroblast-like. Expression of various receptor tyrosine kinases and some ligands suggests an autocrine or paracrine role of these proteins in the pathogenesis of the intimal occlusive lesion in PVS.

Original languageEnglish (US)
Pages (from-to)91-99
Number of pages9
JournalCardiovascular Pathology
Volume15
Issue number2
DOIs
StatePublished - Mar 2006

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Receptor Protein-Tyrosine Kinases
Tunica Intima
Actins
Smooth Muscle
Vascular Endothelial Growth Factor Receptor-1
Fibroblast Growth Factor Receptors
Vascular Endothelial Growth Factor Receptor-2
Platelet-Derived Growth Factor alpha Receptor
Proto-Oncogene Proteins c-kit
Platelet-Derived Growth Factor beta Receptor
Platelet-Derived Growth Factor Receptors
Muscles
Vascular Endothelial Growth Factor Receptor
Desmin
Myofibroblasts
S100 Proteins
Antibodies
Epidermal Growth Factor Receptor
Catheters
Macrophages

Keywords

  • Myofibroblasts
  • Pulmonary vein stenosis
  • Receptor tyrosine kinases

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pathology and Forensic Medicine

Cite this

Riedlinger, W. F. J., Juraszek, A. L., Jenkins, K. J., Nugent, A. W., Balasubramanian, S., Calicchio, M. L., ... Collins, T. (2006). Pulmonary vein stenosis: Expression of receptor tyrosine kinases by lesional cells. Cardiovascular Pathology, 15(2), 91-99. https://doi.org/10.1016/j.carpath.2005.11.006

Pulmonary vein stenosis : Expression of receptor tyrosine kinases by lesional cells. / Riedlinger, Wolfram F J; Juraszek, Amy L.; Jenkins, Kathy J.; Nugent, Alan W.; Balasubramanian, Sowmya; Calicchio, Monica L.; Kieran, Mark W.; Collins, Tucker.

In: Cardiovascular Pathology, Vol. 15, No. 2, 03.2006, p. 91-99.

Research output: Contribution to journalArticle

Riedlinger, WFJ, Juraszek, AL, Jenkins, KJ, Nugent, AW, Balasubramanian, S, Calicchio, ML, Kieran, MW & Collins, T 2006, 'Pulmonary vein stenosis: Expression of receptor tyrosine kinases by lesional cells', Cardiovascular Pathology, vol. 15, no. 2, pp. 91-99. https://doi.org/10.1016/j.carpath.2005.11.006
Riedlinger, Wolfram F J ; Juraszek, Amy L. ; Jenkins, Kathy J. ; Nugent, Alan W. ; Balasubramanian, Sowmya ; Calicchio, Monica L. ; Kieran, Mark W. ; Collins, Tucker. / Pulmonary vein stenosis : Expression of receptor tyrosine kinases by lesional cells. In: Cardiovascular Pathology. 2006 ; Vol. 15, No. 2. pp. 91-99.
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