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

Mark W. Geraci, Mark Moore, Tracy Gesell, Michael E. Yeager, Lori Alger, Heiko Golpon, Bifeng Gao, James E. Loyd, Rubin M. Tuder, Norbert F. Voelkel

Research output: Contribution to journalArticle

203 Citations (Scopus)

Abstract

Primary pulmonary hypertension (PPH) is a disease of unknown etiology characterized by lumen-obliterating endothelial cell proliferation and vascular smooth muscle hypertrophy of the small precapillary pulmonary arteries. Because the vascular lesions are homogeneously distributed throughout the entire 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 meaningful 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 characteristic 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 obtained from 6 patients with primary pulmonary hypertension (PPH) - including 2 patients with the familial form of PPH (FPPH) - and from 6 patients with histologically normal lungs. For the data analysis, gene clusters were generated and the gene expression pattern differences between PPH and normal lung tissue and between PPH and FPPH lung tissue were compared. All PPH lung tissue samples showed a decreased expression of genes encoding several kinases and phosphatases, whereas several oncogenes and genes coding for ion channel proteins were upregulated in their expression. Importantly, we could distinguish by pattern comparison between sporadic PPH and FPPH, because alterations in the expression of transforming growth factor-β receptor III, bone 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 better characterization and understanding of the pathobiology of the distinct clinical phenotypes of pulmonary hypertension.

Original languageEnglish (US)
Pages (from-to)555-562
Number of pages8
JournalCirculation Research
Volume88
Issue number6
StatePublished - Mar 30 2001
Externally publishedYes

Fingerprint

Microarray Analysis
Gene Expression
Lung
Genes
MAP Kinase Kinase 5
Familial Primary Pulmonary Hypertension
Apolipoprotein C-III
Laminin Receptors
Growth Factor Receptors
Transforming Growth Factors
Multigene Family
Oligonucleotide Array Sequence Analysis
Ion Channels
Vascular Smooth Muscle
Oncogenes
Transcriptome
Phosphoric Monoester Hydrolases
Pulmonary Hypertension
Hypertrophy
Pulmonary Artery

Keywords

  • Familial primary pulmonary hypertension
  • Lung tissue
  • Microarray gene profiling
  • Primary pulmonary hypertension

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Geraci, M. W., Moore, M., Gesell, T., Yeager, M. E., Alger, L., Golpon, H., ... Voelkel, N. F. (2001). Gene expression patterns in the lungs of patients with primary pulmonary hypertension: A gene microarray analysis. Circulation Research, 88(6), 555-562.

Gene expression patterns in the lungs of patients with primary pulmonary hypertension : A gene microarray analysis. / Geraci, Mark W.; Moore, Mark; Gesell, Tracy; Yeager, Michael E.; Alger, Lori; Golpon, Heiko; Gao, Bifeng; Loyd, James E.; Tuder, Rubin M.; Voelkel, Norbert F.

In: Circulation Research, Vol. 88, No. 6, 30.03.2001, p. 555-562.

Research output: Contribution to journalArticle

Geraci, MW, Moore, M, Gesell, T, Yeager, ME, Alger, L, Golpon, H, Gao, B, Loyd, JE, Tuder, RM & Voelkel, NF 2001, 'Gene expression patterns in the lungs of patients with primary pulmonary hypertension: A gene microarray analysis', Circulation Research, vol. 88, no. 6, pp. 555-562.
Geraci MW, Moore M, Gesell T, Yeager ME, Alger L, Golpon H et al. Gene expression patterns in the lungs of patients with primary pulmonary hypertension: A gene microarray analysis. Circulation Research. 2001 Mar 30;88(6):555-562.
Geraci, Mark W. ; Moore, Mark ; Gesell, Tracy ; Yeager, Michael E. ; Alger, Lori ; Golpon, Heiko ; Gao, Bifeng ; Loyd, James E. ; Tuder, Rubin M. ; Voelkel, Norbert F. / Gene expression patterns in the lungs of patients with primary pulmonary hypertension : A gene microarray analysis. In: Circulation Research. 2001 ; Vol. 88, No. 6. pp. 555-562.
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AU - Alger, Lori

AU - Golpon, Heiko

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