High blood pressure, or hypertension, affects more than a billion people worldwide and remains the leading cause of death due to heart disease.
Many people rely on common medications like ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) to manage their blood pressure.
These drugs target a system in the body called the renin-angiotensin system (RAS), which helps control blood pressure.
But even with these medicines, most people still struggle to keep their blood pressure under control. This shows there’s a strong need for new and affordable treatment options.
A new study from researchers at the University of Pennsylvania, published in Hypertension Research, explores a different approach. The scientists looked into a powerful enzyme called ACE2, which naturally helps lower blood pressure.
Previously, ACE2 had shown positive results when injected in patients with metabolic or heart-related diseases. In this new study, the researchers wanted to test whether taking ACE2 by mouth could work too—especially when added to the common drugs many people already use.
Dr. Henry Daniell, one of the lead authors of the study, explained that no one had previously looked closely at how these standard blood pressure medications might affect ACE2.
ACE2 plays a balancing role in the RAS system: while ACE leads to the creation of angiotensin II, a substance that tightens blood vessels and raises blood pressure, ACE2 reduces angiotensin II by turning it into angiotensin1-7, which helps relax the blood vessels and lower pressure.
To test their idea, the team used a special oral form of ACE2, developed using a plant-based system involving lettuce. They gave this to pet dogs with a heart condition called myxomatous mitral valve disease—dogs that also had high blood pressure and were already taking ACE inhibitors or ARBs.
Since these were household pets, the researchers couldn’t stop the dogs’ existing treatments. Instead, they gave the ACE2 supplement on top of their regular medication.
What happened next surprised the team. They discovered that ACE inhibitors were blocking the effects of the ACE2 they had added. In other words, the very drugs meant to help lower blood pressure were stopping the new ACE2 treatment from doing its job.
Even more unexpected was the finding that ARBs, another class of common blood pressure medicine, actually increased the amount of angiotensin II—the very substance that ACE2 is supposed to reduce.
This created a problem. “You don’t want to inhibit ACE2, and you don’t want to increase angiotensin II,” said Dr. Daniell. But that’s exactly what happened when these medicines were combined.
However, there was a small silver lining: one ACE inhibitor called lisinopril—widely used in the United States—had a much weaker effect on blocking ACE2 compared to other drugs in the same group.
These findings are important, especially for people already taking ACEIs or ARBs. Many patients could benefit from ACE2, which has also been shown to protect the heart and lungs.
In fact, ACE2 became well known during the COVID-19 pandemic because it also plays a role in how the coronavirus enters the body. The virus reduces ACE2 activity, which may explain why COVID-19 can lead to severe lung and heart problems.
The team now plans to repeat their experiment in dogs that are only taking lisinopril to see if oral ACE2 will work better in that setting. Their ultimate goal is to bring this treatment to humans.
Thanks to FDA approval, they can now begin clinical trials using their plant-based delivery system. This makes ACE2 the first human protein made in plants to be cleared for testing in humans by the FDA.
Dr. Daniell’s passion for this research goes beyond science—he wants to make life-saving treatments more affordable. Most biologic drugs, especially injectable ones, can cost billions of dollars to develop. By using plant-based systems like lettuce, his team hopes to create effective treatments at a fraction of the cost.
In summary, this study highlights both the promise and the challenges of using ACE2 as a new treatment for high blood pressure. It also raises important questions about how current medications might interfere with new therapies.
With further research and trials, this approach could lead to safer, more effective, and more affordable options for millions of people living with heart disease around the world.
If you care about blood pressure, please read studies about blood pressure drug that may increase risk of sudden cardiac arrest, and these teas could help reduce high blood pressure.
For more information about health, please see recent studies about nutrient that could strongly lower high blood pressure, and results showing this novel antioxidant may help reverse blood vessels aging by 20 years.
The research findings can be found in Hypertension Research.
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