Scientists discovered that a protein called AhR, which helps our bodies get rid of toxins, may also play a big role in heart disease. When researchers removed this protein from mice prone to heart disease and fed them an unhealthy diet, something surprising happened: the mice developed much smaller blockages in their arteries and had lower cholesterol levels. The study also found that certain genetic variations in humans related to this protein are connected to cholesterol and triglyceride levels. This discovery opens up new possibilities for treating heart disease by targeting this protein, though more research is needed to understand exactly how it works.
The Quick Take
- What they studied: Whether removing a detoxification protein called AhR from the body could reduce heart disease and improve cholesterol levels in mice
- Who participated: Two groups of genetically modified mice: one group with heart disease (Apoe-/- mice) and another group with both heart disease and no AhR protein (Apoe-/-Ahr-/- mice). Both groups ate an unhealthy Western-style diet for 12 weeks
- Key finding: Mice without the AhR protein developed significantly smaller arterial blockages and had much lower cholesterol and triglyceride levels compared to mice with the protein, despite having more white blood cells circulating in their blood
- What it means for you: This research suggests that blocking the AhR protein might be a new way to treat heart disease by improving cholesterol levels. However, this is early-stage research in mice, and much more testing is needed before any treatments could be developed for humans
The Research Details
Researchers used two groups of specially bred mice that are prone to developing heart disease. One group had the normal version of the AhR protein, while the other group had this protein completely removed. Both groups ate an unhealthy diet similar to what many people eat (high in fat and cholesterol) for 12 weeks to trigger heart disease development.
After 12 weeks, the scientists examined the mice’s arteries to measure how much plaque (fatty buildup) had formed. They also tested their blood to check cholesterol, triglycerides, and inflammation markers. The researchers looked at liver tissue under a microscope and used advanced genetic testing to understand which genes were turned on or off in the livers of each group.
Finally, the scientists performed a large human genetic study looking at thousands of people to see if genetic variations in the AhR gene were connected to cholesterol problems in real people.
This research approach is important because it combines animal studies with human genetic data. By studying mice, scientists can control every variable and see cause-and-effect relationships that would be impossible to study in humans. Then, by checking if the same genetic patterns appear in human populations, they can determine whether the mouse findings might be relevant to people
This study was published in a well-respected scientific journal focused on heart and blood vessel disease. The researchers used multiple approaches (animal studies, genetic analysis, and human data) to support their findings, which strengthens confidence in the results. However, the study was conducted in mice, which don’t always behave the same way as humans. The exact mechanisms explaining why removing AhR helps aren’t fully understood yet, which is an important limitation
What the Results Show
The most striking finding was that mice without the AhR protein developed much smaller plaques (fatty blockages) in their arteries compared to mice with the protein, even though both groups ate the same unhealthy diet. This was surprising because the mice without AhR actually had more white blood cells in their blood, which usually indicates more inflammation and would be expected to make heart disease worse.
The mice without AhR also had significantly lower cholesterol and triglyceride levels in their blood. When researchers examined the liver tissue, they found that mice without AhR accumulated less fat in their livers, suggesting that this protein plays an important role in how the body stores and processes fats.
Genetic analysis of the liver tissue showed that removing AhR affected many genes involved in fat metabolism and processing. This suggests that AhR controls a whole network of genes related to how the body handles cholesterol and other fats.
When researchers looked at human genetic data, they found that people with certain variations in the AhR gene tended to have higher or lower cholesterol and triglyceride levels, supporting the idea that this protein affects fat metabolism in humans too
The study identified specific signaling pathways (cellular communication systems) that were affected when AhR was removed. These pathways control how cells process and store fats. The researchers also noted that while removing AhR increased circulating white blood cells, this didn’t result in worse heart disease, suggesting that the improvement in fat metabolism was more important than the increase in immune cells
Previous research had shown that AhR is mainly known for helping the body eliminate toxins. This study reveals a new and unexpected role for AhR in controlling how the body handles cholesterol and fats. While other studies have suggested AhR affects immune function, this research demonstrates that its role in fat metabolism may be even more important for heart disease development
This study was conducted entirely in mice, and mouse biology doesn’t always match human biology perfectly. The researchers don’t yet fully understand the exact mechanisms explaining why removing AhR improves cholesterol levels. The human genetic study only showed associations between AhR variations and cholesterol levels, not proof of cause-and-effect. Additionally, the study didn’t test whether blocking AhR in adult mice (after heart disease develops) would help, only whether removing it from birth would prevent disease
The Bottom Line
Based on this research, there is currently no recommendation for people to change their behavior. This is early-stage research that suggests a potential new treatment target. Future research will need to determine if drugs that block AhR could safely treat heart disease in humans. Until then, the best ways to prevent heart disease remain: eating a healthy diet low in saturated fat, exercising regularly, maintaining a healthy weight, and not smoking
This research is most relevant to scientists and doctors working on new heart disease treatments. People with high cholesterol or family history of heart disease should be aware of this emerging research but should continue following their doctor’s current recommendations. This is not yet applicable to general health decisions
This research is in the very early stages. Even if blocking AhR proves helpful in additional animal studies, it typically takes 5-10 years or more to develop and test a new drug in humans before it could become available as a treatment
Want to Apply This Research?
- Track weekly cholesterol and triglyceride levels (if available through home testing or regular blood work) alongside diet quality scores to establish personal baseline patterns and monitor response to dietary changes
- Users could use the app to log daily adherence to a heart-healthy diet (Mediterranean or DASH diet style) and track how dietary choices correlate with available lipid markers, while staying informed about emerging research like this study
- Establish a 12-week monitoring period (matching the study duration) to track diet quality, exercise, and any available lipid measurements, then compare results to personal baseline to identify which lifestyle factors most effectively improve cholesterol levels
This research describes early-stage laboratory findings in mice and should not be interpreted as medical advice or a basis for treatment decisions. The findings have not been tested in humans, and no drugs targeting AhR are currently approved for treating heart disease. If you have concerns about heart disease risk or cholesterol levels, please consult with your healthcare provider about appropriate screening and treatment options. Do not stop or change any current heart disease medications without medical supervision.