Chest
Volume 131, Issue 3, March 2007, Pages 850-855
Journal home page for Chest

Original Research: Pulmonary Hypertension
Platelet-Derived Growth Factor Is Increased in Pulmonary Capillary Hemangiomatosis

https://doi.org/10.1378/chest.06-1680Get rights and content

Abstract

Background:Pulmonary capillary hemangiomatosis (PCH) is a rare cause of pulmonary arterial hypertension with no effective medical therapy and a high risk of mortality. The pathogenesis of PCH is unknown.

Methods:We used gene expression analysis to compare lung tissue samples from two patients with PCH to those from seven control subjects. The nodules of proliferating capillaries in PCH patients were needle microdissected from cryostat sections. RNA extraction and labeling were followed by hybridization to U95Av2 oligonucleotide arrays (Affymetrix; Santa Clara, CA).In situhybridization and immunohistochemistry were also performed.

Results:The gene expression profile of PCH allowed for unsupervised clustering from the profile of the lung tissue samples of control subjects. Platelet-derived growth factor (PDGF)-B gene (PDGFB), PDGF receptor (PDGFR)-β gene (PDGFR-β), mast cell-related genes, and type 2 pneumocyte-related genes were found to be overexpressed in PCH lesions.In situhybridization as well as immunohistochemistry for PDGFB showed expression by type 2 pneumocytes and endothelial cells. Immunohistochemical staining for PDGFR-β localized to pericytic/vascular smooth muscle cells surrounding the proliferating capillaries. CD117 staining confirmed an abundance of mast cells in the lesions, which also stained heavily for PDGFR-β.

Conclusions:The expression of thePDGFBandPDGFR-β genes characterizes the nodular proliferations of PCH. Increased numbers of mast cells, pericytes, and type II pneumocytes accompany the endothelial proliferation. The up-regulation of these important angiogenic and antiapoptotic genes suggests a mechanism and potential therapeutic approaches for PCH.

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Materials and Methods

We obtained lung tissue samples from two patients with PCH and normal lung tissue from seven patients who had undergone lobectomies performed for neoplastic disease. These control subjects were similar to those in the single published microarray study of PAH.10

Results

High-power histologic examination showed that the alveolar septa exhibited proliferations of capillary-sized vessels on both sides of the alveolar wall, giving a nodular appearance (Fig 1). Small and large muscular pulmonary arteries showed hypertensive changes, including intimal and medial thickening without plexiform lesions.

Unsupervised clustering performed using a list of 7,567 genes filtered for low expression showed two groups within the data set, corresponding to the PCH case patients

Discussion

PCH has been reclassified as a form of PAH associated with significant venous or capillary involvement.11PCH has a peak incidence in the second and third decade, affecting men and women equally.2Most cases appear sporadic, with one report of familial occurrence.12Imaging with chest radiography and CT scanning shows nodular pulmonary infiltrates, septal lines, lymphadenopathy, and occasional pleural effusions, distinguishing PCH from other forms of PAH13, 14; however, a definitive diagnosis can

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    This research was supported in part by the Department of Pathology, Columbia University College of Physicians and Surgeons, and National Institutes of Health grant HL67771.

    The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

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