Assaad Adel M, Kawut Steven M, Arcasoy Selim M, Rosenzweig Erika B, Wilt Jessie S, Sonett Joshua R, Borczuk Alain C
Departments of Pathology, Columbia University College of Physicians and Surgeons, New York, NY.
Medicine, Columbia University College of Physicians and Surgeons, New York, NY.
Chest. 2007 Mar;131(3):850-855. doi: 10.1378/chest.06-1680.
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.
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 situ hybridization and immunohistochemistry were also performed.
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)-beta gene (PDGFR-beta), mast cell-related genes, and type 2 pneumocyte-related genes were found to be overexpressed in PCH lesions. In situ hybridization as well as immunohistochemistry for PDGFB showed expression by type 2 pneumocytes and endothelial cells. Immunohistochemical staining for PDGFR-beta 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-beta.
The expression of the PDGFB and PDGFR-beta 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.
肺毛细血管瘤病（PCH）是肺动脉高压的一种罕见病因，尚无有效的药物治疗方法，且死亡率高。PCH的发病机制尚不清楚。
我们使用基因表达分析来比较两名PCH患者的肺组织样本与七名对照受试者的肺组织样本。从低温恒温器切片中对PCH患者增殖性毛细血管结节进行针吸显微切割。进行RNA提取和标记，随后与U95Av2寡核苷酸阵列（Affymetrix；加利福尼亚州圣克拉拉）杂交。还进行了原位杂交和免疫组织化学检测。
PCH的基因表达谱能够与对照受试者肺组织样本的谱进行无监督聚类。发现血小板衍生生长因子（PDGF）-B基因（PDGFB）、PDGF受体（PDGFR）-β基因（PDGFR-β）、肥大细胞相关基因和Ⅱ型肺细胞相关基因在PCH病变中过度表达。PDGFB的原位杂交以及免疫组织化学显示Ⅱ型肺细胞和内皮细胞有表达。PDGFR-β的免疫组织化学染色定位于增殖性毛细血管周围的周细胞/血管平滑肌细胞。CD117染色证实病变中有大量肥大细胞，这些肥大细胞也强烈表达PDGFR-β。
PDGFB和PDGFR-β基因的表达是PCH结节性增殖的特征。内皮细胞增殖伴随着肥大细胞、周细胞和Ⅱ型肺细胞数量的增加。这些重要的血管生成和抗凋亡基因的上调提示了PCH的一种机制和潜在治疗方法。
