Skin, and the proteins that regulate it, could play a significant role in controlling blood pressure and other risk factors that leave heart patients predisposed to cardiovascular disease.

In a study published in the scientific journal eLife, lead author Randall S. Johnson, PhD, and colleagues demonstrated through rodent models that skin is key to keeping both blood pressure and heart rate in check through its reaction with the amount of oxygen available in any given environment. Though Johnson et al.’s initial trials were performed in mice, they believe the results to be true for humans, as well.

“Vertebrates confront the world chiefly through skin,” Johnson and co-authors wrote in the paper. “As a reflection of how different vertebrates adapt to the environment, skin structure varies to a significant degree from one vertebrate class to another, and even within classes.” Mammalian skin, the researchers said, is among the most complex forms of skin in vertebrates.

Though it’s established that blood pressure is a risk factor for cardiovascular disease, the authors wrote that, in most cases, doctors aren’t sure of its cause. If a patient has high blood pressure, they’re suffering from reduced blood flow through small vessels in the skin and other areas of the body, Johnson and colleagues noted, and blood flow to oxygen-deprived tissues is regulated by HIF proteins, which are present in skin tissue.

Johnson and his co-authors exposed mice to low-oxygen conditions, noting how their bodies—and their skin—reacted to the high-risk environment.

“Our study was set up to understand the feedback loop between skin and the cardiovascular system,” Johnson said in a release from the University of Cambridge, where he works as a physiology professor. “By working with mice, we were able to manipulate key genes involved in this loop.”

The team found that mice who lacked either HIF-1a or HIF-2a proteins in their skin reacted differently to oxygen starvation than normal mice, exhibiting changes in heart rate, blood pressure, activity levels and skin temperature. These mice experienced a rise in blood pressure and heart rate in the first 10 minutes of exposure to dangerous conditions, then saw a dramatic decrease in both that dipped below normal levels and lasted up to 36 hours. By the time these mice hit the 48-hour mark, the authors wrote, their vitals were back to normal.

It appeared a lack of HIF proteins, or proteins controlled by HIFs, “dramatically” changed the way skin reacted to oxygen deprivation.

“These findings suggest that our skin’s response to low levels of oxygen may have substantial effects on how the heart pumps blood around the body,” first author Andrew Cowburn, MD, said in the release. “Low oxygen levels—whether temporary or sustained—are common and can be related to our natural environment or to factors such as smoking and obesity. We hope that our study will help us better understand how the body’s response to such conditions may increase our risk of—or even cause—hypertension.”