Gene expression patterns in the lungs of patients with primary pulmonary hypertension - A gene microarray analysis

Primary pulmonary hypertension (PPH) is a disease of unknown etiology chara cterized by lumen-obliterating endothelial cell proliferation and vascular smooth muscle hypertrophy of the small precapillary pulmonary arteries. Bec ause the vascular lesions are homogeneously distributed throughout the enti re lung, we propose that a tissue fragment of the lung is representative of the whole lung. RNA extracted from the fragments is likely to provide mean ingful information regarding the changes in gene expression pattern in PPH when compared with structurally normal lung tissue. We hypothesize that the lung tissue gene expression pattern of patients with PPH has a characteris tic profile when compared with the gene expression pattern of structurally normal lungs and that this characteristic gene expression profile provides new insights into the pathobiology of PPH. Using oligonucleotide microarray technology, we characterized the expression pattern in the lung tissue obt ained from 6 patients with primary pulmonary hypertension (PPH)-including 2 patients with the familial form of PPH (FPPH)-and from 6 patients with his tologically normal lungs. For the data analysis, gene clusters were generat ed and the gene expression pattern differences between PPH and normal lung tissue and between PPH and FPPH lung tissue were compared. All PPH lung tis sue samples showed a decreased expression of genes encoding several kinases and phosphatases, whereas several oncogenes and genes coding for ion chann el proteins were upregulated in their expression. Importantly, we could dis tinguish by pattern comparison between sporadic PPH and FPPH, because alter ations in the expression of transforming growth factor-beta receptor III. b one morphogenic protein 2, mitogen-activated protein kinase kinase 5, RACK 1, apolipoprotein C-III, and the gene encoding the laminin receptor 1 were only found in the samples from patients with sporadic PPH, but not in FPPH samples. We conclude that the microarray gene expression technique is a new and useful molecular tool that provides novel information pertinent to a b etter characterization and understanding of the pathobiology of the distinc t clinical phenotypes of pulmonary hypertension.