Ultrasound up-regulates expression of heme oxygenase-1 gene in endothelial cells

Purpose: We found heme oxygenase-1 (HO-1) gene up-regulation in response to ultrasound stimulation in endothelial cells. This project was started to explore the mechanism since it could be applied clinically. Methods: Quantitative real-time PCR experiments were conducted to determine the appropriate condition to up-regulate HO-1 gene expression. A promoter assay experiment and a microarray analysis were done to analyze signal transduction pathways to be activated in endothelial cells by ultrasound stimulation. Results: Approximately, 33-fold up-regulation of HO-1 mRNA was observed when endothelial cells were exposed to 1-MHz ultrasound at 0.3 W/cm² and DF 10 % for 20 s. Data obtained from promoter analysis and microarray analysis suggested that the Nrf2/StRE signal pathway was involved in the up-regulation. In addition, ultrasound stimulation to endothelial cells changed its gene expression profile so that it could modify the anti-inflammatory, antioxidant, and vasodilatory activities in addition to pro-angiogenic and vascular reconstitution activities of endothelial cells. Conclusion: It was suggested that ultrasound stimulation of endothelial cells up-regulated HO-1 expression through intracellular oxidative stress, which subsequently changed the gene expression pattern so that it could modify vascular functions.