Graphical abstract. Credit: DOI: 10.1016/j.cmet.2021.07.015Katrien De Bock, ETH Zurich professor, and her team discovered a type of blood vessel cell that grows rapidly in muscle tissue. This allows for the formation of new blood vessels. This discovery could be used by researchers to develop new therapies for muscle vascular disorders.Katrien De Bock states that in industrialized countries, surgeons are often forced to amputate a leg or foot because of impaired vascular supply to the muscles and nerves of diabetic patients. She is Professor of Exercise and Health at ETH Zurich and studies how to treat vascular diseases in the muscles and new blood vessels. It is well-known that sport and exercise stimulate the formation blood vessels. However, little information is available about the molecular and cell mechanisms that underlie these blood vessels. De Bock states, "Once these mechanisms are understood, we can work towards improving patient's blood supply."De Bock and her collaborators have studied the effects of exercise on the formation and maintenance of thin blood vessels in muscle. They also used cultured human cells. They turned the spotlight on the cells of the vascular walls (also known as endothelial) and discovered two types of capillary endothelial cells. These can be distinguished using the molecular marker ATF4. It turned out that cells with low levels of ATF4 tend to be found in capillaries that supply white muscle fibers. Cells with high levels of ATF4 form primarily part of blood vessels near red muscle fibers.Are you ready to go?The scientists also demonstrated that exercise stimulates the cell division of endothelial and muscle cells with high levels ATF4 (those close to red muscle fibers), which leads to the formation new capillaries. Exercise does not produce a direct response in cells that have very low levels of ATF4. De Bock states that endothelial cells containing high levels ATF4 are in a metabolic standby mode, always ready to form new vessels. ATF4 is a regulator protein within the cell. This protein is a regulatory protein within the cell. It primes cells to respond quickly to the right stimulus. These cells are primed to respond quickly to the appropriate stimulus as soon as a person, in this instance a mouse, starts exercising. They increase their amino acid intake, accelerate the formation DNA and proteins, and encourage cell proliferation. This eventually leads to the formation new blood vessels.It is unknown why these "ready to go" endothelial cells are found primarily near red muscle fibers. This mystery will be solved next by the researchers. The scientists also hope to use their findings to create therapies to stimulate the growth muscle blood vessels in patients with diabetes and arterial occlusions, as well as transplant recipients.Continue readingZheng Fan and colleagues, Exercise-induced Angiogenesis is dependent upon metabolically primed ATF3/4+ cells, Cell Metabolism (2021). Information from Cell Metabolism Zheng Fan and colleagues, Exercise-induced Angiogenesis is dependent upon metabolically primed endothelial cells ATF3/4+, (2021). DOI: 10.1016/j.cmet.2021.07.015
