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Left Atrial Stenosis Induced Pulmonary Venous Arterialization and Group 2 Pulmonary Hypertension in Rat
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Pulmonary vein stenosis: expression of receptor tyrosine kinases by lesional cells

Wolfram F J Riedlinger1, Amy L Juraszek, Kathy J Jenkins

  • 1Department of Pathology, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.

Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology
|March 15, 2006
PubMed
Abstract

Insights

Infant pulmonary vein stenosis (PVS) involves intimal cells that are myofibroblast-like, expressing growth factor receptors. This suggests these proteins play a role in PVS lesion development, impacting treatment effectiveness.

Area of Science:

  • Pediatric cardiology
  • Vascular biology
  • Cellular pathology

Background:

  • Primary pulmonary vein stenosis (PVS) is a serious infant disorder.
  • Restenosis significantly limits the effectiveness of current PVS treatments like catheter intervention and chemotherapy.
  • The cellular origin of the occlusive intimal lesions in PVS remains unclear.

Observation:

  • Seven infant PVS cases were analyzed using immunohistochemistry.
  • Antibodies targeted smooth muscle markers, cell lineage markers, and receptor tyrosine kinases (RTKs).
  • Specific RTKs investigated included PDGFR, EGFR, FGFR, VEGFR, and c-kit.

Findings:

  • Lesional cells in PVS strongly expressed smooth muscle actin (SMA) and muscle-specific actin (MSA).
  • These cells did not express markers for macrophages, lymphocytes, or endothelial cells, nor Ki-67.
  • Significant expression of PDGFR-alpha/beta, FGFR, and VEGFR-2 was observed, with phosphorylated PDGF beta receptor.

Implications:

  • The intimal cells in PVS are identified as myofibroblast-like based on their smooth muscle marker expression.
  • The expression of RTKs and ligands suggests autocrine or paracrine signaling pathways are involved in PVS pathogenesis.
  • Understanding these cellular mechanisms could lead to improved therapeutic strategies for PVS and restenosis.

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