Grant: Operating Grant

The human body is constantly subjected to low oxygen conditions (hypoxia) in everyday living. Exercise, cold temperatures and changes in altitude all effect the oxygen concentration in our body's tissues and organs. For survival, we must adapt to these changes in oxygen. Fortunately, our body is highly able to respond quickly and efficiently to hypoxia. A large number of genes important for survival are finely controlled by oxygen through a protein complex called hypoxia-inducible factor (HIF-1). These genes play a critical role in blood vessel development, growth and maintenance and have been shown to be involved in different vascular pathologies. Given the possible importance of HIF-1 in cardiovascular disease, understanding of how HIF-1 is controlled can lead to beneficial effects. Since its conception, our laboratory has been studying how HIF-1 activity is controlled in cells and tissues. We have found that in addition to hypoxia, different hormones can increase HIF-1 and hypoxic genes in cells isolated from blood vessels. We are convinced that this type of gene induction of is important in how blood vessels react in the normal healthy body and in various disease situations. We believe that changes in the normal regulation of this factor could cause major blood vessel problems and lead to hypertension, vascular remodeling atherosclerosis and other vascular diseases. The goal of our work is to understand the mechanisms involved in this type of HIF-1 regulation, to evaluate the genes that are activated and to demonstrate the importance of this regulation of HIF-1 in vascular biology. When the pathways are well mapped out, we hope that this knowledge will identify targets to help fight cardiovascular disease.