Research shows that removing the MPST enzyme in mice prone to high cholesterol paradoxically reduced their blood cholesterol levels and plaque buildup in arteries. According to Gram Research analysis of this 2026 study, mice lacking both the Apoe gene and MPST enzyme had significantly lower total cholesterol, LDL cholesterol, and triglycerides compared to mice with only the Apoe gene removed. This unexpected finding suggests blocking MPST might be a new way to fight heart disease, though human studies are needed to confirm whether this approach would work in people.
Scientists discovered something surprising about how our bodies handle cholesterol and heart disease. According to Gram Research analysis, when researchers removed a specific enzyme called MPST in mice prone to heart disease, the animals had lower cholesterol levels and less plaque buildup in their arteries. This finding is unexpected because the enzyme normally helps produce hydrogen sulfide, a chemical messenger in the body. The results suggest that blocking this particular enzyme might be a new way to protect against heart disease, though much more research is needed before this could help people.
Key Statistics
A 2026 research study in mice found that removing the MPST enzyme reduced total cholesterol, LDL cholesterol, and triglycerides in animals prone to high cholesterol, compared to animals without MPST removal.
Mice lacking both the Apoe gene and MPST enzyme showed significantly reduced atherosclerotic plaque formation in their aortas compared to mice with only the Apoe gene removed, according to the 2026 study.
The 2026 research found that MPST removal decreased hepatic apolipoprotein B expression, a protein responsible for transporting cholesterol in the blood, without altering other major cholesterol-producing enzymes.
The Quick Take
- What they studied: Whether removing an enzyme called MPST could reduce cholesterol levels and heart disease in mice that are genetically prone to these conditions
- Who participated: Four groups of laboratory mice: normal mice, mice missing only MPST, mice missing only the Apoe gene (prone to high cholesterol), and mice missing both Apoe and MPST. All mice ate a high-fat diet similar to Western fast food for 14 weeks
- Key finding: Mice missing both Apoe and MPST had significantly lower cholesterol, LDL (bad cholesterol), and triglycerides (blood fats) compared to mice missing only Apoe. These mice also developed less plaque in their arteries, the main sign of heart disease
- What it means for you: This research suggests that blocking the MPST enzyme might be a new strategy to lower cholesterol and reduce heart disease risk. However, this was only tested in mice, so it’s too early to know if it would work in people. Anyone with high cholesterol should continue following their doctor’s current treatment recommendations
The Research Details
Researchers created four groups of mice with different genetic backgrounds. One group was normal, one had only the MPST enzyme removed, one had only the Apoe gene removed (making them prone to high cholesterol and heart disease), and one had both genes removed. All mice ate a high-fat diet for 14 weeks to mimic unhealthy eating patterns. After 14 weeks, scientists measured cholesterol levels in the blood, looked at plaque buildup in the arteries, and examined how the liver was working.
This type of study is called a genetic knockout study. Scientists remove specific genes to understand what those genes do in the body. By comparing the four groups, researchers could see exactly what happened when MPST was removed in mice that already had high cholesterol problems.
The researchers measured several important things: total cholesterol, LDL cholesterol (the bad kind), triglycerides (another type of blood fat), and the amount of plaque in the aorta (the main artery from the heart). They also looked at liver tissue to see how fat was being stored and which enzymes were active.
This research approach is important because it helps scientists understand which genes and enzymes control cholesterol and heart disease. By using mice with specific genes removed, researchers can test whether blocking a particular enzyme actually causes the improvements they see. This is much more controlled than just observing what happens naturally. The findings could eventually lead to new medicines that block MPST to help people with high cholesterol
This study was published in a peer-reviewed scientific journal, meaning other experts reviewed the work before publication. The researchers used a standard mouse model (C57BL/6 background) that is commonly used in similar studies, making the results easier to compare with other research. However, the study only tested mice, not people, so results may not directly apply to humans. The sample size of mice in each group was not specified in the abstract, which makes it harder to evaluate the statistical strength of the findings
What the Results Show
The main finding was surprising and counterintuitive. When researchers removed the MPST enzyme in mice that were already prone to high cholesterol (Apoe knockout mice), the animals actually had lower cholesterol levels, not higher. Specifically, mice missing both Apoe and MPST had decreased total cholesterol, LDL cholesterol, and triglycerides compared to mice missing only Apoe.
The reduction in blood fats correlated with less plaque buildup in the aorta, the main artery leaving the heart. This is important because plaque buildup is the hallmark of atherosclerosis, the disease that leads to heart attacks and strokes. The mice with both genes removed showed significantly reduced atherosclerotic lesions compared to mice with only the Apoe gene removed.
Researchers also found that the liver was producing less apolipoprotein B (ApoB), a protein that packages cholesterol for transport in the blood. Lower ApoB levels help explain why these mice had lower cholesterol and triglycerides. Interestingly, other enzymes involved in making cholesterol and fatty acids remained unchanged, suggesting that MPST affects cholesterol through a specific pathway rather than broadly shutting down fat production.
The study found that hydrogen sulfide production was reduced in the liver of double knockout mice, confirming that MPST removal successfully decreased this signaling molecule. However, the expression of two other enzymes that produce hydrogen sulfide (CBS and CSE) was not altered, meaning the body did not compensate by making more of these enzymes. Fat storage in the liver was not significantly different among the four groups of mice, suggesting that MPST removal specifically affects cholesterol transport rather than fat accumulation in liver cells
Previous research showed that removing a different hydrogen sulfide-producing enzyme (CSE) actually accelerated plaque formation and worsened atherosclerosis. This new finding with MPST is paradoxical, meaning it goes against what researchers expected based on prior studies. The results suggest that different hydrogen sulfide-producing enzymes may have opposite effects on heart disease, which is an important new insight. This discovery challenges the simple idea that more hydrogen sulfide is always protective and suggests the body’s chemistry is more complex than previously thought
This study only tested mice, not humans, so the results may not directly apply to people. The specific number of mice in each group was not provided, making it difficult to assess the statistical power of the findings. The study only looked at mice eating a high-fat diet for 14 weeks, so it’s unclear whether these results would hold true for different diets or longer time periods. The research did not test whether blocking MPST in normal mice (without the Apoe gene removed) would have similar effects. Additionally, the study did not examine whether blocking MPST might have negative effects on other body systems or functions
The Bottom Line
This research is preliminary and only conducted in mice. Current evidence-based recommendations for managing cholesterol and heart disease remain unchanged: eat a healthy diet low in saturated fat, exercise regularly, maintain a healthy weight, and follow your doctor’s advice about medications like statins if prescribed. Do not change your treatment based on this mouse study. If you have high cholesterol or heart disease risk, discuss your individual situation with your healthcare provider. This research may eventually lead to new treatments, but that is years away
This research is most relevant to scientists studying cholesterol metabolism and heart disease, and to pharmaceutical companies developing new treatments. People with high cholesterol or family history of heart disease should be aware of this emerging research but should not expect immediate clinical applications. Healthcare providers may find this research interesting for understanding the biology of cholesterol, but it does not change current treatment guidelines. This research is not yet relevant for making personal health decisions
This is very early stage research. Even if these findings are confirmed in additional mouse studies, it typically takes 10 to 15 years of research before a new drug based on these findings could be tested in people. If a drug were eventually developed, it would need to go through multiple phases of human testing before approval. Realistic timeline for any clinical application: 10 to 20 years at minimum
Frequently Asked Questions
Can blocking the MPST enzyme help lower cholesterol in people?
This research only tested mice, so it’s too early to know if it would work in humans. Scientists would need to conduct many more studies before testing this approach in people. Current cholesterol treatments like statins remain the evidence-based option for now
What is the MPST enzyme and why does it matter for heart disease?
MPST is an enzyme that produces hydrogen sulfide, a chemical messenger in the body. This 2026 study found that removing MPST unexpectedly reduced cholesterol and heart disease in mice, suggesting this enzyme may be a new target for future heart disease treatments
How does removing MPST lower cholesterol if it produces a protective molecule?
Hydrogen sulfide was thought to be protective based on previous research, but this study shows MPST’s role is more complex. Removing MPST specifically reduced apolipoprotein B production, which packages cholesterol for transport in blood, explaining the cholesterol reduction
Should I ask my doctor about MPST-blocking drugs for my high cholesterol?
No MPST-blocking drugs currently exist for humans. This is basic research in mice. Continue following your doctor’s current treatment plan with proven medications and lifestyle changes. Discuss any new research with your doctor, but don’t expect clinical applications for many years
Why is this finding called paradoxical?
Previous research showed that removing a different hydrogen sulfide-producing enzyme worsened heart disease. This study found the opposite with MPST removal, which was unexpected. The paradox shows that different enzymes affecting hydrogen sulfide have opposite effects on cholesterol
Want to Apply This Research?
- Track your cholesterol levels (total cholesterol, LDL, HDL, and triglycerides) every 3 to 6 months if you have high cholesterol or heart disease risk. Record the date, values, and any changes to diet or medications. This creates a personal trend line to discuss with your doctor
- Use the app to set and monitor heart-healthy habits: aim for 150 minutes of moderate exercise per week, reduce saturated fat intake, increase fiber from vegetables and whole grains, and maintain a healthy weight. Log daily meals and exercise to see patterns over time
- Create a long-term tracking dashboard showing cholesterol trends, diet quality, exercise frequency, and weight over months and years. Set reminders for regular cholesterol tests and doctor appointments. Share this data with your healthcare provider to guide treatment decisions
This article summarizes research conducted in laboratory mice and does not represent medical advice for humans. The findings have not been tested in people and may not apply to human health. If you have high cholesterol, heart disease, or cardiovascular risk factors, consult your healthcare provider about appropriate treatment options. Do not change your current medications or treatment plan based on this research. This study is preliminary and much additional research is needed before any clinical applications could be developed.
This research translation is published by Gram Research, the science division of Gram, an AI-powered nutrition tracking app.