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

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.