Korean Circ J.  2008 Jan;38(1):51-59. 10.4070/kcj.2008.38.1.51.

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

• Park DW
• Song JM
• Han KH
• Lee CW
• Kang DH
• Lee SD
• Joo SJ
• Song H
• Lee JW
• Song JK

• KMID: 2225874
• DOI: http://doi.org/10.4070/kcj.2008.38.1.51

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 upregulated 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.

Keyword

Pulmonary hypertension; Genes; Lung

MeSH Terms

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

Figure

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

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  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.

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  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.

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