South SFV Today

Researchers have linked the CXCL12 gene to the development of a critical coronary artery in a recent study published in the journal Cell. This study marks a significant advancement toward Stanford's long-term goal to foster medical revascularization, which involves developing a treatment for blocked or limited-flow arteries by growing new ones.

“For the first time, we have evidence of a gene that regulates the development of one of the most important types of arteries in the human body,” said Kristy Red-Horse, co-senior author of the study and a biology professor at Stanford School of Humanities and Sciences. The study explores the potential of regrowing certain arteries by reintroducing their developmental pathways in a diseased heart.

The research indicates that the gene CXCL12 is associated with the formation of the posterior descending artery. This artery carries oxygenated blood to the back of the heart and typically branches from the right main coronary artery in about 80% of humans. However, it can also branch from the left main artery or from both.

Red-Horse collaborated with Tim Assimes, an associate professor of cardiovascular medicine in the Stanford School of Medicine, who utilized data from the Department of Veterans Affairs’ Million Veteran Program. This program includes medical information from more than 60,000 veterans who have undergone angiograms. The researchers found ten DNA locations tied to the development of the artery on the back of the heart, with the strongest being CXCL12.

“We now have evidence that this patterning of our two major coronary arteries is controlled by differences in our DNA code we inherit from our parents, and the top signal is near a gene that is also responsible for the growth and development of coronary arteries,” said Assimes.

Further experiments showed that reducing the protein linked to CXCL12 in mice led to the development of different artery patterns. The implications of having a right-dominant artery pattern on heart disease protection remain unresolved.

Looking forward, the researchers plan to explore the DNA variants affecting CXCL12 expression and aim to develop a therapeutic treatment by targeting gene activation to foster new collateral arterial branches.

Red-Horse and Assimes, along with other Stanford collaborators—including Shoa Clarke, Xiaochen Fan, and others—contributed to the study. External collaborators hailed from institutions like the National Research Council in Cagliari, Italy, the University of California, San Diego, and the University of Pennsylvania Perelman School of Medicine.

The research was supported by the VA, National Institutes of Health, Howard Hughes Medical Institute, Doris Duke Foundation, and a gift from the Smilow family. The findings bring hope for less invasive treatments than current surgical and mechanical interventions like bypass surgery and stent placements.

For further information, Stanford School of Humanities and Sciences provided contact through Sara Zaske.