The Role of Sirtuin-2 in Tubular Forming Activity of Human Umbilical Vein

Sirtuin proteins have emerged as important modulators of several age-associated diseases. These in-clude cancer and diabetes, as well as cardiovascular and neurodegenerative diseases. Among the sir-tuin family members, SIRT2 mRNA is strongly expressed. To investigate the pathophysiological sig-nificance of SIRT2 as a primary regulator of angiogenesis, we focused on the biological role of SIRT2 under hypoxic conditions, examining the gene expression pattern of sirtuin family members in human umbilical vein endothelial cells (HUVECs). SIRT2 was expressed primarily in the cytoplasm, but it was dynamically trans-localized in the nuclear by hypoxia stimuli. Interestingly, both SIRT2 and the pro-angiogenic factor, VEGF, were up- regulated by hypoxia. A Matrigel assay demonstrated that the HUVECs formed a tube-like structure under hypoxia. The SIRT2 inhibitor, AK-1, significantly de-creased the tube-forming activity of the HUVECs under either normoxia or hypoxia conditions. These findings suggest that SIRT2 might be a key regulator of angiogenesis