Pulmonary Venous Hypertension Causes Differential Expression Of Developmental Genes In The Lung

Pulmonary venous hypertension (PVH) is a frequent consequence of left sided heart disease and causes extensive lung vascular remodeling which leads to right ventricular failure. Functional genomics underlying this structural remodeling in PVH are unknown but present potential targets for therapeutic strategies. Developmental genes have been implicated in the pathophysiology of lung cancer and asthma but their role in vascular remodeling and pulmonary hypertension is unclear. PVH was induced in rats by supracoronary aortic banding 8 weeks prior to investigations. For genomic analyses, RNA was extracted from isolated lungs of control and PVH rats and whole rat genome microarrays were performed. Out of 31100 arrayed genes, 231 were significantly up- or downregulated more than 3-fold in PHV. These comprised genes involved in vascular regulation and inflammation such as ETB receptor, heme oxygenase 1 and interleukin-1 alpha but also developmental genes like frizzled related protein, Jun D and semaphorin 6A. Differential expression of selected genes was verified by RT-PCR and confirmed by Western Blot and 2D-PAGE. PVH causes differential expression of genes involved in vascular regulation and development. Functional effects of this genomic regulation may contribute to the pathology of PVH and suggest a potential role for developmental genes in vascular remodeling. Sponsored by EU-IP “Pulmotension”