Researchers from the University of Texas Health Science Center at Houston (UTHealth) helped uncover a protective role for octamer-binding transcriptional factor 4 (OCT4), important for embryonic stem cell (ESC) self-renewal, against plaque build-up in the walls of arteries that supply blood to the heart.
The study, “Activation of the ESC pluripotency factor OCT4 in smooth muscle cells is atheroprotective,” was published in the June issue of Nature Medicine, a premier scientific journal.
Using mice models of atherosclerosis, the researchers found the animals lacking OCT4 displayed increased plaque size and reduced plaque stability, as shown by a thinner fibrous cap, increased necrotic core area, and reduction in the number of smooth muscle cells (SMCs). The finding represents the first evidence that OCT4 protects against heart disease.
The team extended the relevance of the findings to humans by analyzing coronary artery specimens collected from sixteen patients with atherosclerotic lesions. While the sample size was not large enough to meet American Heart Association criteria, the importance of OCT4 in the lesions was confirmed.
“The discovery could lead to a new treatment for the condition affecting millions of people in the United States and around the world. It could also help in the treatment of stroke,” said study coauthor Dr. Yong-Jian Geng, a professor of medicine at UTHealth, in a press release.
Previously, OCT4 was primarily known for its impact on regenerative medicine and stem cell therapy because of its ability to assist the generation of induced pluripotent stem cells (iPSCs). For many research studies, iPSCs can be used in place of ESCs, of which is surrounded in ethical concerns and controversy.
Researchers applauded the collaborative efforts of UTHealth and the University of Virginia (UVA) School of Medicine.
“Reproducibility of the data is a very important issue in modern science. Therefore, it was extremely important for us (for the paper) that Dr. Geng’s group independently, and using different methods, was able to get the same results about mechanisms of activation of this gene (OCT4) in smooth muscle cells,” said Olga A. Cherepanova, first author of the study and a UVA faculty member.
Preliminary evidence pointed toward the relevance of OCT4 for atherosclerosis prevention in humans. Future research could uncover the mechanism by which OCT4 is regulated, and identify therapeutic targets that promote plaque stabilization and prevent disease progression.