Gene helps prevent heart attack, stroke—and may offer way to block effects of aging

May 17, 2016, University of Virginia
An atherosclerotic lesion. Such lesions can rupture and cause heart attacks and strokes. Credit: UVA School of Medicine

A gene that scientific dogma insists is inactive in adults actually plays a vital role in preventing the underlying cause of most heart attacks and strokes, researchers at the University of Virginia School of Medicine have determined. The discovery opens a new avenue for battling those deadly conditions, and it raises the tantalizing prospect that doctors could use the gene to prevent or delay at least some of the effects of aging.

"Finding a way to augment the expression of this gene in may have profound implications for promoting health and possibly reversing some of the detrimental effects with aging," said researcher Gary K. Owens, PhD, director of UVA's Robert M. Berne Cardiovascular Research Center.

Unexpected Protective Effect

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: Owens and his colleagues have determined the gene plays a critical protective role during the formation of 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," said Olga A. Cherepanova, PhD, a senior research scientist in Owens' lab.

One surprising finding from UVA's research: When the researchers blocked the effect of Oct4 in mice, they thought the atherosclerotic plaques might become smaller, because of the reduced number of inside. Instead, the plaques grew larger, less stable and more dangerous, stuffed with lipids, dead cells and other damaging components.

Advancing Regenerative Medicine

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 - 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 in Owens' lab.

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.

The UVA researchers suspect that at least some of the detrimental effects of aging, including the increased possibility of a rupture, stem from a decrease in the body's ability to reactivate Oct4. "Finding a way to reactivate this pathway may have 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 . Who knows, this may end up being the 'fountain-of-youth gene,' a way to revitalize old and worn-out . Only time will tell."

Explore further: Fundamental beliefs about atherosclerosis overturned

More information: Olga A Cherepanova et al, Activation of the pluripotency factor OCT4 in smooth muscle cells is atheroprotective, Nature Medicine (2016). DOI: 10.1038/nm.4109

Related Stories

Fundamental beliefs about atherosclerosis overturned

July 6, 2015
Doctors' efforts to battle the dangerous atherosclerotic plaques that build up in our arteries and cause heart attacks and strokes are built on several false beliefs about the fundamental composition and formation of the ...

Protein kinase Akt identified as arbiter of cancer stem cell fate, paper reports

December 20, 2012
(Medical Xpress)—The protein kinase Akt is a key regulator of cell growth, proliferation, metabolism, survival, and death. New work on Akt's role in cancer stem cell biology from the lab of senior author Honglin Zhou, MD, ...

Recommended for you

Genetic link discovered between circadian rhythms and mood disorders

August 15, 2018
Circadian rhythms are regular 24-hour variations in behaviour and activity that control many aspects of our lives, from hormone levels to sleeping and eating habits.

Ovarian cancer genetics unravelled

August 14, 2018
Patterns of genetic mutation in ovarian cancer are helping make sense of the disease, and could be used to personalise treatment in future.

New genome-editing strategy could lead to therapeutics

August 14, 2018
Researchers at UMass Medical School have developed a genome-editing strategy to correct disease-causing DNA mutations in mouse models of human genetic diseases, according to research published in the Aug. 18 edition of Nature ...

Study reveals broad 'genetic architectures' of traits and diseases

August 13, 2018
Scientists at Johns Hopkins Bloomberg School of Public Health have developed a powerful method for characterizing the broad patterns of genetic contributions to traits and diseases. The new method provides a "big picture" ...

Genetic tools uncover cause of childhood seizure disorder missed by other methods

August 13, 2018
Early childhood seizures result from a rare disease that begin in the first months of life. Researchers at University of Utah Health have developed high-tech tools to uncover the genetic cause of the most difficult to diagnose ...

Researchers predict risk for common deadly diseases from millions of genetic variants

August 13, 2018
A research team at the Broad Institute of MIT and Harvard, Massachusetts General Hospital (MGH), and Harvard Medical School reports a new kind of genome analysis that could identify large fractions of the population who have ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.