Research shows that a liver protein called HDAC9 promotes high cholesterol and heart disease by blocking the body’s natural cholesterol removal system. According to Gram Research analysis, when scientists blocked HDAC9 in mice, their cholesterol levels dropped and arterial plaque buildup decreased. HDAC9 works by suppressing CYP7A1, an enzyme that converts cholesterol into bile acids for elimination. This finding suggests future medicines targeting HDAC9 could offer a new way to treat high cholesterol, though human studies are needed.
Scientists discovered that a protein called HDAC9 in your liver makes it harder for your body to get rid of cholesterol. When researchers blocked this protein in mice, their cholesterol levels dropped and they had less buildup in their arteries. According to Gram Research analysis, this finding could lead to new medicines that target the liver to help people with high cholesterol. The study shows that HDAC9 works by turning off another protein that helps your body eliminate cholesterol through bile acids, which are digestive fluids your liver makes.
Key Statistics
A 2026 research study found that blocking the HDAC9 protein in mice with high cholesterol restored production of CYP7A1, the key enzyme responsible for converting cholesterol into bile acids for removal from the body.
Laboratory research published in 2026 showed that HDAC9 knockdown in human liver cells prevented cholesterol accumulation even when exposed to high levels of fatty acids, while HDAC9 overexpression made cholesterol buildup worse.
A 2026 study in mice demonstrated that HDAC9 promotes atherosclerosis independently of inflammation, revealing a completely separate mechanism for how this protein contributes to heart disease beyond previously known inflammatory pathways.
The Quick Take
- What they studied: Whether a liver protein called HDAC9 causes high cholesterol and heart disease by blocking the body’s natural cholesterol removal system
- Who participated: Laboratory mice genetically modified to have high cholesterol, plus human liver cells grown in dishes. No human participants were directly involved in this research.
- Key finding: Blocking HDAC9 in the liver restored the body’s cholesterol-removal system, lowering blood cholesterol levels and reducing fatty buildup in arteries by activating a key enzyme called CYP7A1
- What it means for you: This research suggests future medicines could target HDAC9 to help people with high cholesterol, but human studies are needed before any new treatment becomes available. This is early-stage research, not yet ready for patients.
The Research Details
Researchers used two main approaches to understand HDAC9’s role in cholesterol. First, they studied mice with genetic changes that made them prone to high cholesterol and heart disease. They fed these mice a high-fat diet and watched what happened to their HDAC9 levels and cholesterol removal. Second, they tested HDAC9 in human liver cells grown in laboratory dishes to understand the exact mechanism.
The team used two methods to block HDAC9: a drug called TMP195 and a genetic technique called AAV8-shHdac9 that turned off the HDAC9 gene specifically in the liver. They measured cholesterol levels, bile acid production, and fatty buildup in arteries to see if blocking HDAC9 helped.
This combination of animal studies and cell experiments allowed researchers to both see the real-world effects and understand the molecular mechanism—how HDAC9 actually works at the cellular level.
This research approach is important because it moves beyond just showing that HDAC9 is involved in cholesterol problems. By testing both blocking the protein and turning off its gene, researchers confirmed that HDAC9 itself causes the problem, not just something associated with it. Testing in both mice and human cells makes the findings more likely to be relevant to people. Understanding the exact mechanism (that HDAC9 blocks CYP7A1) gives scientists a clear target for developing new medicines.
This study has several strengths: it uses multiple methods to block HDAC9, tests in both animal and human cells, and identifies the specific mechanism. However, it’s important to note this is laboratory research, not human clinical trials. The findings in mice don’t always translate directly to humans. The study was published in a peer-reviewed scientific journal, meaning other experts reviewed the work before publication. No human participants were involved, so we don’t yet know if these results will work in real patients.
What the Results Show
When researchers blocked HDAC9 in mice with high cholesterol, several important things happened. First, the mice’s livers started making more CYP7A1, which is the key enzyme that converts cholesterol into bile acids—the body’s way of getting rid of excess cholesterol. Second, the mice’s blood cholesterol levels dropped significantly. Third, the fatty buildup (plaque) in their arteries decreased, which is the main problem in heart disease.
The researchers tested this in two ways: using a drug to block HDAC9 and using genetic techniques to turn off the HDAC9 gene specifically in the liver. Both methods worked, suggesting that HDAC9 in the liver is the main problem. When they tested human liver cells in dishes, blocking HDAC9 prevented cholesterol from building up inside the cells, even when exposed to high levels of fatty acids.
Most importantly, the researchers proved that HDAC9 works by directly controlling the CYP7A1 gene. When they blocked HDAC9 but also turned off CYP7A1, the cholesterol-lowering benefit disappeared. This proves that HDAC9 must work through CYP7A1 to affect cholesterol levels.
The study found that HDAC9 levels increased in the liver when mice ate a high-fat diet, suggesting that unhealthy eating triggers the problem. The research also showed that HDAC9 works independently of inflammation—meaning it lowers cholesterol through a different pathway than previously thought. This is significant because it identifies a completely new way to treat high cholesterol that doesn’t rely on anti-inflammatory approaches.
Previous research showed that HDAC9 contributes to heart disease by causing inflammation. This study reveals a new, separate mechanism: HDAC9 also directly interferes with cholesterol removal. This is important because it means blocking HDAC9 could help in two ways—reducing inflammation and improving cholesterol metabolism. The finding that HDAC9 controls CYP7A1 is novel and wasn’t previously understood. This research builds on earlier work showing that bile acid metabolism is important for heart health, but identifies HDAC9 as a new control point.
This research was conducted in mice and laboratory cells, not in humans. Mice don’t always respond the same way humans do to treatments. The study didn’t test the HDAC9-blocking drug or genetic approach in humans, so we don’t know if it will be safe or effective in people. The researchers used mice with genetic modifications that don’t naturally occur in humans, which may not perfectly represent human cholesterol problems. The study focused on the liver’s role in cholesterol removal but didn’t examine other factors that affect cholesterol, like diet or exercise. Long-term effects of blocking HDAC9 weren’t studied, so we don’t know if benefits persist or if side effects develop over time.
The Bottom Line
Based on this research, there are no new treatments to recommend yet. This is early-stage laboratory research. People with high cholesterol should continue following their doctor’s advice about current medications (like statins), diet, and exercise. However, this research suggests that future medicines targeting HDAC9 in the liver could become a new treatment option. Anyone interested in this research should discuss it with their doctor but should not expect new treatments based on this work for several years.
This research is most relevant to people with high cholesterol or heart disease risk, and to researchers developing new cholesterol medications. People taking current cholesterol medications don’t need to change anything based on this study. This research is particularly interesting for people who don’t respond well to current treatments, as it suggests a completely new approach. Pharmaceutical companies developing new drugs should pay attention to HDAC9 as a potential target.
This research is at an early stage. Typically, it takes 5-10 years or more to develop a new drug from laboratory research to human testing. If HDAC9-targeting drugs are developed, they would need to go through multiple phases of human clinical trials before becoming available. Realistic timeline: new treatments based on this research, if they happen, would likely not be available for at least 5-7 years.
Frequently Asked Questions
What is HDAC9 and why does it matter for cholesterol?
HDAC9 is a protein in your liver that controls how your body gets rid of cholesterol. Research shows it blocks the enzyme CYP7A1, which converts cholesterol into bile acids for elimination. When HDAC9 is active, cholesterol builds up; when it’s blocked, cholesterol levels drop.
Can I take a medicine to block HDAC9 right now?
No, not yet. This is early laboratory research in mice and cells. Scientists have identified HDAC9 as a potential drug target, but human clinical trials haven’t started. It typically takes 5-10 years to develop a new medicine from this stage of research.
Does this research mean I should change my cholesterol medication?
No. Continue taking your current cholesterol medications as prescribed by your doctor. This research doesn’t affect existing treatments. It suggests future treatment options that may become available years from now, but doesn’t change current medical recommendations.
How does blocking HDAC9 lower cholesterol differently than current drugs?
Current cholesterol drugs like statins block cholesterol production. This research targets HDAC9 to improve cholesterol removal through bile acids. It’s a different pathway that could potentially work alongside or instead of current treatments, offering new options for people who don’t respond well to existing drugs.
Will this research help people with genetic cholesterol problems?
Possibly. People with genetic high cholesterol often don’t respond well to current treatments. Since this research identifies a new mechanism for cholesterol control, HDAC9-targeting drugs might help these patients. However, human studies are needed to confirm this benefit.
Want to Apply This Research?
- Track your cholesterol levels (total, LDL, and HDL) every 3-6 months through your doctor’s blood tests. Record the dates and values in the app to monitor trends over time and see how diet and lifestyle changes affect your numbers.
- Use the app to log high-fat meals and track how they affect your energy and digestion. This helps you understand your personal response to diet and prepares you for future conversations with your doctor about cholesterol management strategies.
- Set monthly reminders to log your cholesterol test results and any changes in how you feel. Track lifestyle factors like exercise, sleep, and stress alongside cholesterol numbers to identify patterns. Share this data with your doctor at annual checkups to inform treatment decisions.
This research is laboratory-based and has not been tested in humans. The findings in mice do not guarantee the same results in people. This article describes early-stage research and should not be interpreted as medical advice or a recommendation to change your current cholesterol treatment. Anyone with high cholesterol should continue following their doctor’s recommendations and taking prescribed medications. Do not stop or change any cholesterol medication without consulting your healthcare provider. This research suggests potential future treatments but no new medicines are currently available based on these findings. Always consult with a qualified healthcare professional before making any changes to your cholesterol management plan.
This research translation is published by Gram Research, the science division of Gram, an AI-powered nutrition tracking app.