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 the UVA researchers are the first to provide conclusive evidence of that: they have determined 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 says the author.

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.

The reactivation of Oct4 within smooth muscle cells was associated with hydroxymethylation of the Oct4 promoter and was hypoxia inducible factor-1α (HIF-1α, encoded byHIF1A) and Krüppel-like factor-4 (KLF4)-dependent. 

While UVA's research has focused on how Oct4 offers cardiovascular protection, Owens and his colleagues 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.

Oct4 is one of the "stem cell pluripotency factors" described by Shinya Yamanaka, MD, PhD, for which he received the 2012 Nobel Prize. His lab and many others have shown that artificial over-expression of Oct4 within somatic cells grown in a lab dish is essential for reprogramming these cells into induced pluripotential stem cells, which can then develop into any cell type in the body or even an entire organism.

http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.4109.html