A and B, and endothelial converting enzyme (ECE) are altered in the lungs of Sprague-Dawley rats at 16 weeks after left coronary artery ligation. We now sought to determine the effect of SERCA2a gene therapy on gene expression of these mediators in the lung. Methods Gene expression of components of the ET-1 pathway, MCP-1 and IL-6 were investigated in whole lungs of rats at 16 weeks after LCA, at 16 weeks post LCA with tail vein injection of adenoassociated viral (AAV) gene transfer of SERCA2a

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... t 12 weeks post LCA, or sham procedure(n=5 in each group). Lungs were snap frozen in liquid nitrogen, RNA extracted using a modified Trizol and RN easy protocol and gene expression determined in reverse transcribed cDNA by qPCR. Results Expression of ET-1, ETAR, MCP-1 and IL-6 genes were elevated in heart failure animals and reduced to or towards normal in SERCA2a treated animals. In heart failure animals there was a trend towards reduced ETRB expression which was significantly improved by SERCA2a gene therapy (figure 1 ). ECE gene expression was not altered by LCA or gene therapy. Conclusion SERCA2a gene therapy directed at the myocardium in heart failure also affects gene expression in the lungs of CHF animals. This may provide therapeutic benefit to the lungs in addition, reducing inflammation and stimuli associated with structural and vascular remodelling.