Pluripotency Factor Oct4 in Atherosclerosis and Aging

Oct4 is one of the factors used in reprogramming recipes that convert ordinary somatic cells into induced pluripotent stem cells, similar to embryonic stem cells and capable of generating any tissue type given the right environment and further programming. Given this, it is not entirely unexpected for Oct4 to show up in mechanisms relevant to aging and regeneration, as is the case here. Researchers have found Oct4 to have a protective role in the development of atherosclerosis, stabilizing the plaques that form in blood vessels over the course of that condition. As a target for therapy this leaves a lot to be desired - it is very far down the line of disease progression, and stable plaques still grow and narrow blood vessels, producing high blood pressure, remodeling of the vascular system, and other aspects of cardiovascular disease. It would be far better to note this research as interesting and focus instead on better ways to remove plaques and prevent their existence in the first place.

The gene, Oct4, plays a key role in the development of all living organisms, but scientists have, until now, thought it was permanently inactivated after embryonic development. Some controversial studies have suggested it might have another function later in life, but a new study is the first to provide conclusive evidence of that. The gene plays a critical protective role during the formation of atherosclerotic plaques inside blood vessels. The rupturing of these plaques is the underlying cause of many heart attacks and strokes. The researchers found that Oct4 controls the movement of smooth muscle cells into protective fibrous "caps" inside the plaques - caps that make the plaques less likely to rupture. The researchers also have provided evidence that the gene promotes many changes in gene expression that are beneficial in stabilizing the plaques. This is exciting, because studies suggest that it may be possible to develop drugs or other therapeutic agents that target the Oct4 pathway as a means to reduce the incidence of heart attacks or stroke. "Our findings have major implications regarding possible novel therapeutic approaches for promoting stabilization of atherosclerotic plaques." One surprising finding: when the researchers blocked the effect of Oct4 in mice, they thought the atherosclerotic plaques might become smaller, because of the reduced number of smooth muscle cells inside. Instead, the plaques grew larger, less stable and more dangerous, stuffed with lipids, dead cells and other damaging components.

Researchers believe the gene could also prove critical to the field of regenerative medicine, which investigates the growth and replacement of tissues and organs. The researchers believe that Oct4 and its family of target genes are activated in other somatic cells - the non-reproductive cells in the body - and play a key role in the cells' ability to repair damage and heal wounds. Studies to test this are under way. Researchers suspect that at least some of the detrimental effects of aging, including the increased possibility of a plaque rupture, stem from a decrease in the body's ability to reactivate Oct4. "Finding a way to reactivate this pathway may have profound implications for health and aging. 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."