Grant: Operating Grant - PA: Musculoskeletal Health, Arthritis, Skin and Oral Health

Most cells in the body require oxygen for survival and to perform their specialized functions. Muscle cells rely heavily on oxygen to contract and perform activity. Oxygen is carried from the heart to the muscle through arteries. Oxygen then is distributed to each and every cell in the muscle through a network of tiny blood vessels, the capillaries. A number of cardiovascular diseases involve insufficient blood supply to leg muscles, which results in a range of debilitating effects, from exercise intolerance to limb amputation. In these diseases, the blood vessels become dysfunctional and they do not respond to normal growth cues. It is possible that this failure to respond approrpiately is due to the increased level of factors that inhibit blood vessel growth. FoxO1 is a protein that stimulates many negative processes, including stopping cells from multiplying, and causing cell death. This research proposal focuses on assessing the role of FoxO1 in acting as a negative regulator of new blood vessel growth. These studies will help us to establish a better understanding of ways in which blood vessels can be stimulated to grow in muscles that lack sufficient blood flow, thus providing potential therapeutic options for people with peripheral vascular disease.