As an embryonic stem cell pluripotency factor, Oct4 was previously thought to only be active in embryos, not in adults. However, novel findings from the University of Virginia School of Medicine provided, for the first time, solid proof that Oct4 is not permanently irrelevant after the embryo stage.
Gary K. Owens, PhD, and his research time discovered that fully understanding the role of Oct4 in adulthood actually has potential for preventing heart attacks and treating survivors with gene manipulation.
"Finding a way to augment the expression of this gene in adult cells may have profound implications for promoting health and possibly reversing some of the detrimental effects with aging," Owens said.
They found that Oct4 expression leads to the production of protective fibrous “caps” inside of atherosclerotic plaques, controlling the smooth muscle cells inside the plaques and preventing them from rupturing. This stabilizing role could be critical for the survival of people with plaque formation, because plaque ruptures cause heart attacks and stroke.
Additionally, the researchers experimented with blocking the expression of Oct4, expected the plaques to reduce in volume due to the lack of smooth muscle cell “caps” inside of the plaques. However, the plaques grew larger, less stable, and more dangerous, clearly demonstrating how important Oct4 expression is for preventing dangerous cardiovascular events.
From their results, the researchers suspect that an increased risk of plaque rupture causing heart disease and stroke later in life is due to a reduction in the body’s ability to reactivate Oct4.
"Finding a way to reactivate this pathway may have profound implications for health and aging," Owens said. "We think this is just the tip of the iceberg for controlling plasticity of somatic cells, and this could impact many human diseases and the field of regenerative medicine.”
Indeed, targeting the Oct4 pathway is a promising option for future drug development, especially for people at a high risk for heart attack or stroke.
The study was recently published in the journal Nature Medicine.
Source: University of Virginia Health System