TY - JOUR
T1 - Pulmonary vein stenosis
T2 - Expression of receptor tyrosine kinases by lesional cells
AU - Riedlinger, Wolfram F J
AU - Juraszek, Amy L.
AU - Jenkins, Kathy J.
AU - Nugent, Alan W.
AU - Balasubramanian, Sowmya
AU - Calicchio, Monica L.
AU - Kieran, Mark W.
AU - Collins, Tucker
N1 - Funding Information:
Sowmya Balasubramanian's work was partially supported by the “Christina Capozzi Foundation.” Supported by NIH grants P50 HL74734 and ROI HL035716, and by the Eric and Kathy Kobren Fund.
PY - 2006/3
Y1 - 2006/3
N2 - 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.
AB - 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.
KW - Myofibroblasts
KW - Pulmonary vein stenosis
KW - Receptor tyrosine kinases
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U2 - 10.1016/j.carpath.2005.11.006
DO - 10.1016/j.carpath.2005.11.006
M3 - Article
C2 - 16533697
AN - SCOPUS:33644879750
SN - 1054-8807
VL - 15
SP - 91
EP - 99
JO - Cardiovascular Pathology
JF - Cardiovascular Pathology
IS - 2
ER -