pISSN 1738-5520 eISSN 1738-5555
Indexed in PubMed, SCIE and Scopus
Open Access, Peer-reviewed, Monthly
    Korean Circ J. 2008 Jan;38(1):51-59. Korean.
    Published online Jan 31, 2008.
    https://doi.org/10.4070/kcj.2008.38.1.51
    Copyright © 2008 The Korean Society of Cardiology
    Original Article

    Different Gene Expression Patterns in the Lungs of Patients with Secondary Pulmonary Hypertension

    Duk-Woo Park, MD,1 Jong-Min Song, MD,1 Ki-Hoon Han, MD,1 Cheol Whan Lee, MD,1 Duk-Hyun Kang, MD,1 Sang-Do Lee, MD,2 Suk-Jung Joo, MD,3 Hyun Song, MD,3 Jae Won Lee, MD,3 and Jae-Kwan Song, MD1
      • 1Division of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
      • 2Division of Pulmonology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
      • 3Division of Cardiac Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
    • Correspondence: Jae-Kwan Song, MD, Divisions of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736, Korea. Tel: 82-2-3010-3150, Fax: 82-2-486-5918, Email: jksong@amc.seoul.kr
    Received July 27, 2007; Revised October 01, 2007; Accepted November 16, 2007.

    Abstract

    Background and Objectives

    Despite the similar degree of pressure or volume overloading, the development of secondary pulmonary hypertension (PH) shows diverse variability among individual patients.

    Subjects and Methods

    Using microarray technology, we compared the gene expression pattern of the lung tissues in 13 patients with secondary PH due to congenital shunt (pulmonary arterial hypertension, PAH, n=6) or valvular heart disease (pulmonary venous hypertension, PVH, n=7) with 5 normal subjects.

    Results

    As compared to the normal controls, secondary PH showed a decreased expression of genes encoding transcriptional factors (BHLHB2, EGR3, JUNB, KLF4, KLF6 and MAFF), cytoskeleton protein (VIL2 and XLKD1) and cell differentiation and viability (MCL1, SNF1LK and TNFAIP3). PVH showed an increased expression of genes encoding proliferation of pulmonary capillary endothelial cells (ESM1), cell proliferation (IGFBP2 and BMP6), collagen synthesis (COL4A2 and SERPINH1), and cytoskeleton (TMSL8) as compared with the normal controls. In patients with secondary PH, PVH showed an up-regulated expression of proliferation of pulmonary capillary endothelial cells (ESM1), cell proliferation (EGR2, PLK2 and TNC) and collagen synthesis (COL4A1), and an down-regulated expression of inflammation (IL1RL1, IL7R, CCL5, CCL19, CXCR 6 and XCL1/XCL2) and immune response (IGHM and TRA@; TRAC), as compared with PAH.

    Conclusion

    There were significant differences in the gene expression pattern in secondary PH patients according to the underlying mechanism. A future study is needed to determine the diagnostic and therapeutic implications of these findings.

    Keywords
    Pulmonary hypertension; Genes; Lung

    Figures

    Fig. 1
    MA plotting between control array and experimental array before and after normalization by global scaling method.

    Fig. 2
    Histology of lungs in patients with secondary pulmonary hypertension. Panel A shows preservation of the overall architecture of lung structure in patients with atrial septal defect and severe pulmonary hypertension (grade 1). Panel B shows marked thickening of the vascular media in patients with chronic mitral regurgitation (grade 2). Panel C indicates a severe concentric laminar intimal fibrosis in patients with chronic mitral regurgitation (grade 3). Elastic stain, ×400.

    Fig. 3
    Number of differentially expressed genes (DEG) between secondary pulmonary hypertension and normal subjects (left panel: red circle-DEG by fold change and blue circle-DEG by t-test) and volcano plot (right panel). PAH: pulmonary arterial hypertension, PVH: pulmonary venous hypertension, vol: volcano.

    Tables

    Table 1
    Baseline demographic, hemodynamic and pathologic data

    Table 2
    Number of differentially expressed genes with gene-ontology

    Table 3
    Gene groups with predominant down-regulation in secondary pulmonary hypertension compared with normal subjects

    Table 4
    Gene groups with predominant up-regulation in pulmonary venous hypertension vs. normal subjects

    Table 5
    Gene groups with predominant up-regulation in pulmonary venous hypertension vs. pulmonary arterial hypertension

    Table 6
    Gene groups with predominant down-regulation in pulmonary venous hypertension vs. pulmonary arterial hypertension

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    MeSH Terms
    Cell Differentiation
    Cell Proliferation
    Collagen
    Cytoskeleton
    Endothelial Cells
    Gene Expression
    Heart Valve Diseases
    Humans
    Hydrogen-Ion Concentration
    Hypertension
    Hypertension, Pulmonary
    Inflammation
    Lung
    Metrics
    Share
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