Research reviewed by Gram in a 2026 mouse study found that removing a protein called YAP from artery muscle cells reduced atherosclerosis, the buildup of fatty plaque in arteries. The protein appears to drive plaque growth by switching on angiopoietin-2. Blocking YAP may be a future treatment strategy, but human testing is still needed.
Clogged arteries, called atherosclerosis, build up when muscle cells in artery walls multiply and move into fatty plaques. A new Gram Research analysis of a 2026 study in the Journal of the American Heart Association looked at a protein called YAP, which helps control these cell movements. In mice fed a high-cholesterol diet, YAP levels rose in artery plaques. When researchers removed YAP from the artery muscle cells, the mice developed less plaque buildup. The study also found that YAP works partly by turning on a signal called angiopoietin-2. These results come from animal research, so they do not yet show the same effect in people. Still, they point to YAP as a possible future target for treating heart disease.
Key Statistics
A 2026 mouse study published in the Journal of the American Heart Association found that removing the protein YAP from artery muscle cells reduced atherosclerotic plaque buildup, even in mice fed a high-cholesterol diet.
A 2026 study in mice found that restoring the signaling protein angiopoietin-2 in artery muscle cells completely reversed the plaque-reducing effect of removing YAP.
A 2026 mouse study reported that YAP levels were elevated in artery muscle cells within atherosclerotic plaques compared with healthy artery walls.
The Quick Take
- What they studied: Researchers wanted to know whether a protein called YAP, which controls how artery muscle cells grow and move, plays a role in the buildup of plaque that narrows arteries.
- Who participated: The study used laboratory mice, including mice bred to develop artery plaque and mice given gene-based treatments to raise their cholesterol. The exact number of mice was not listed in the summary, and no human volunteers took part.
- Key finding: Mice that lacked YAP in their artery muscle cells developed less atherosclerosis, even when they ate a high-cholesterol diet. The study found that YAP appears to drive plaque growth by switching on angiopoietin-2, a signaling protein that pushes these cells to multiply and move.
- What it means for you: This research does not change how you should care for your heart today. It does suggest that a future medicine targeting YAP in artery cells could help slow plaque buildup. Heart-healthy habits such as eating well, staying active, and having your cholesterol checked remain the best proven steps for now.
The Research Details
The researchers studied how atherosclerosis, the buildup of fatty plaque inside artery walls, develops in mice. They used two main approaches to create plaque. One group of mice received a gene-delivery treatment that raised their blood cholesterol, and another group had a genetic change that prevents the body from clearing cholesterol well. Both groups were fed a high-cholesterol diet to speed up plaque formation.
To test YAP’s role, the team created mice that lacked YAP only in their smooth muscle cells, the muscle cells that line artery walls. They compared these mice with normal mice to see whether plaque grew differently. The team also grew smooth muscle cells in the lab to study the process step by step, including how the cells changed shape, moved, and multiplied when exposed to a growth signal called platelet-derived growth factor.
Finally, the researchers tested whether angiopoietin-2 was the link between YAP and plaque. They boosted angiopoietin-2 in the artery muscle cells of mice that lacked YAP and checked whether the plaque benefit disappeared. They also looked at a helper protein called TEAD4, which appears to help YAP switch on angiopoietin-2.
Using mice that lack YAP only in artery muscle cells allowed the researchers to test a single cause rather than guess. Because the change was limited to one cell type, the results point to a specific target instead of a general effect on the whole body. Combining whole-animal tests with lab experiments on cells also helps show both what happens and how it happens.
The study used several separate mouse models and lab tests that point in the same direction, which makes the findings more convincing. Reliable research of this kind usually includes control groups, and the design appears to include them. However, this is an early-stage animal study published in a respected heart journal. Its results need to be confirmed by other scientists, and the summary does not list the exact number of mice, which limits how fully readers can judge the statistical strength.
What the Results Show
The researchers found that YAP levels were higher in the artery muscle cells inside plaques than in healthy artery walls. This suggests that YAP becomes more active as plaque forms, which is one reason scientists wanted to test whether it contributes to the disease.
When YAP was removed from artery muscle cells, mice developed less atherosclerosis. This was true in mice given a gene-based treatment to raise cholesterol and in mice with a genetic change that affects cholesterol clearance. In both cases, the plaque-related changes were reduced compared with mice that still had YAP.
The study then showed that YAP works partly through angiopoietin-2. In lab experiments, YAP-deficient muscle cells changed less, and they moved and multiplied less when stimulated with a growth signal. When angiopoietin-2 was boosted again, these cells regained their plaque-forming behavior. In mice, restoring angiopoietin-2 in artery muscle cells completely reversed the protective effect of removing YAP.
Finally, the researchers found that YAP appears to turn on angiopoietin-2 with the help of TEAD4. In simple terms, YAP teams up with TEAD4 to switch on a gene that pushes artery muscle cells to change into a form that builds plaque. The authors concluded that blocking YAP in these cells may be a useful strategy for treating atherosclerosis in the future.
Removing YAP from artery muscle cells changed how these cells behaved, not just how much plaque formed. The cells were less likely to switch into the disease-promoting form, which suggests YAP acts as a control switch for the cell changes that build plaque. This matters because it helps explain why the protective effect appeared even when cholesterol levels were high. Restoring angiopoietin-2 in the artery cells removed the benefit, which supports the idea that this pathway is a central link in the process rather than a side effect.
Scientists have long known that smooth muscle cells in artery walls multiply and migrate during plaque growth. YAP had already been linked to similar cell behaviors in other settings, such as tissue growth and repair. This study adds evidence that YAP plays a specific role in heart disease. Angiopoietin-2 has been studied in blood vessel health and inflammation, so its link to plaque-forming muscle cells fits with what researchers already know about how blood vessels respond to injury.
The most important limitation is that this research was done in mice, and mouse results do not always apply to people. Mouse plaques also develop differently from human plaques, which can take decades to form. The summary does not list how many mice were studied, which makes it harder to judge how reliable the results are. The study also focused on a short list of molecules, so other factors that influence plaque growth were not examined. Finally, no human trials have tested whether blocking YAP is safe or effective, so a treatment based on this work is still years away, if it works at all.
The Bottom Line
Based on this single animal study, the evidence is promising but early. Confidence that YAP contributes to plaque growth in mice is moderate to strong, since several experiments point the same way. Confidence that blocking YAP would help people with heart disease is low right now, because no human studies have tested it. For everyday heart health, the strongest evidence still supports eating less saturated fat and more vegetables, whole grains, and fish, staying physically active, and managing blood pressure and cholesterol with a doctor.
People with a family history of heart disease, high cholesterol, or existing artery plaque may find this research especially interesting, since it points toward possible future treatments. Heart researchers and drug developers may use these findings to explore new targets. Readers looking for a change they can make today should focus on proven steps with their doctor. This study should not change medication use or diet plans on its own.
Turning a lab finding like this into a treatment usually takes many years. Next steps would include testing in larger animal studies, checking whether drugs can safely block YAP, and then running human clinical trials. Even in the best case, people would likely not see a new YAP-based treatment for atherosclerosis for many years. Heart-healthy habits, by contrast, can begin to improve cholesterol and blood pressure within weeks to months.
Frequently Asked Questions
Does blocking YAP stop plaque buildup in arteries?
In a 2026 mouse study, removing YAP from artery muscle cells reduced atherosclerotic plaque growth in mice fed a high-cholesterol diet. Researchers have not yet tested this approach in people, so it is not an established treatment for humans.
What causes clogged arteries to form?
Clogged arteries, called atherosclerosis, form when fatty deposits build up in artery walls. Muscle cells in the artery wall multiply and move into these deposits, which narrows the artery over time. Diet, cholesterol levels, and genetics all influence this process.
What is angiopoietin-2 and how does it relate to heart disease?
Angiopoietin-2 is a signaling protein that helps regulate blood vessel changes. In mouse research, YAP appeared to switch on angiopoietin-2, which pushed artery muscle cells to multiply and move into plaques. Restoring this signal reversed the benefit of removing YAP.
What can I do now to protect my arteries from plaque buildup?
Eating less saturated fat, eating more vegetables, whole grains, and fish, staying physically active, and not smoking are well-supported steps. Ask your doctor about checking your cholesterol and blood pressure, since these are key markers for artery health.
Want to Apply This Research?
- Track weekly averages of your LDL cholesterol, blood pressure, and minutes of moderate activity, using results from your doctor’s visits or a home blood pressure monitor. Log your saturated fat and vegetable servings each day so you can see patterns over time.
- Set one small heart-healthy goal each week, such as adding a serving of vegetables to two meals a day or walking for 10 extra minutes after dinner. Use the app to check off each day you meet the goal, and review your progress every Sunday.
- Review your heart-health data every three months and share the trends with your doctor at regular checkups. Over the long term, watch for steady improvements in cholesterol, blood pressure, and activity levels. Update your goals as your doctor advises, and keep an eye on new research as it develops.
This article summarizes an early-stage study conducted in mice and published in a scientific journal. The findings have not been tested in humans and should not be used to make decisions about medications, diet, or treatment. Please talk with your doctor or another qualified healthcare provider before making any changes to your health routine, especially if you have heart disease, high cholesterol, or other medical conditions.
This research translation is published by Gram Research, the science division of Gram, an AI-powered nutrition tracking app.