A protein called TRIM65 accelerates atherosclerosis by blocking cells’ ability to clean up damaged mitochondria, according to research reviewed by Gram Research. In laboratory studies, mice without TRIM65 developed significantly less arterial plaque and fatty deposits compared to normal mice. This discovery identifies TRIM65 as a potential drug target for preventing heart disease, though human studies are still needed to confirm these findings apply to people.
Scientists discovered that a protein called TRIM65 plays a major role in causing atherosclerosis, the disease where fatty buildup clogs arteries. According to Gram Research analysis, when TRIM65 is present, it stops cells from cleaning up damaged parts of themselves, leading to harmful buildup and inflammation. Researchers used mice and lab cells to show that removing TRIM65 reduced artery damage and fatty deposits. This finding could lead to new treatments that target TRIM65 to prevent heart disease and strokes. The study reveals how a single protein controls a chain reaction that damages blood vessels over time.
Key Statistics
A 2026 research article published in Molecular and Cellular Biochemistry found that TRIM65 protein levels were significantly elevated in atherosclerotic tissue compared to healthy tissue, suggesting a direct role in artery disease development.
Laboratory experiments showed that cells without the TRIM65 protein demonstrated dramatically reduced foam cell formation and increased mitochondrial autophagy compared to normal cells, indicating TRIM65 actively blocks the cell’s natural cleanup mechanisms.
Mice genetically modified to lack TRIM65 showed substantially reduced atherosclerotic plaque burden and lipid accumulation in their blood vessel walls compared to standard atherosclerosis-prone mice, demonstrating the protein’s critical role in disease progression.
The Quick Take
- What they studied: How a protein called TRIM65 contributes to atherosclerosis, the disease where arteries get clogged with fatty deposits
- Who participated: Laboratory mice genetically modified to develop atherosclerosis, plus mouse cells grown in dishes and treated with oxidized cholesterol
- Key finding: Mice without the TRIM65 protein had significantly less artery damage and fatty buildup compared to normal mice, and their cells were better at cleaning up damaged mitochondria
- What it means for you: This research identifies TRIM65 as a potential drug target for preventing or slowing atherosclerosis, though human studies are still needed to confirm these findings apply to people
The Research Details
Researchers created two types of experiments to study atherosclerosis. First, they used special mice that naturally develop clogged arteries when fed a high-fat diet, comparing normal mice to mice without the TRIM65 gene. Second, they grew mouse artery cells in laboratory dishes and exposed them to oxidized cholesterol (a harmful form of cholesterol) to watch how TRIM65 affected cell behavior. They measured changes in protein levels, fatty deposits, and cellular damage markers to understand what TRIM65 was doing at the molecular level.
The scientists focused on a cellular cleanup process called mitophagy, which is like taking out the trash inside cells. When mitochondria (the cell’s energy factories) get damaged, mitophagy removes them before they cause problems. The researchers discovered that TRIM65 interferes with this cleanup process by breaking down the proteins that normally trigger mitophagy.
This combination of animal and cell-based experiments allowed researchers to see both the big picture (how TRIM65 affects whole organisms) and the detailed mechanisms (exactly how TRIM65 works at the molecular level).
Understanding the specific molecular mechanisms behind atherosclerosis is crucial because it helps scientists identify new drug targets. Rather than treating symptoms, targeting TRIM65 could potentially prevent the disease from developing in the first place. This research bridges the gap between basic science and potential clinical applications by showing that removing one problematic protein can have protective effects throughout the entire disease process.
This study combines multiple research approaches (animal models, cell cultures, and molecular analysis) which strengthens the findings. The use of genetically modified mice without TRIM65 provides strong evidence for cause-and-effect relationships. However, because this is laboratory research, results may not directly translate to humans. The study was published in a peer-reviewed scientific journal, meaning other experts reviewed the methods and conclusions. Additional human studies would be needed to confirm these findings apply to people with heart disease.
What the Results Show
The most important discovery was that TRIM65 protein levels were significantly higher in atherosclerotic tissue compared to healthy tissue. When researchers removed the TRIM65 gene from mice, these animals developed much less arterial plaque (the fatty deposits that clog arteries) and had lower levels of lipid accumulation in their blood vessel walls.
In laboratory cell experiments, cells without TRIM65 showed dramatically reduced foam cell formation. Foam cells are the main culprits in atherosclerosis—they’re cells that have absorbed too much cholesterol and become bloated and dysfunctional. The cells without TRIM65 were much better at avoiding this transformation.
The mechanism behind these protective effects involves mitochondrial cleanup. Cells without TRIM65 showed increased mitophagy activity, meaning they were successfully removing damaged mitochondria. In contrast, normal cells with TRIM65 accumulated damaged mitochondria, which generated excessive harmful molecules called reactive oxygen species (ROS). This oxidative stress accelerated the transformation of normal cells into foam cells.
The research revealed that TRIM65 works by degrading two critical proteins called PINK1 and Parkin, which are essential for triggering mitophagy. By destroying these proteins, TRIM65 essentially breaks the cell’s ability to clean up damaged mitochondria. The accumulation of dysfunctional mitochondria then creates a cascade of problems: increased oxidative stress, inflammatory responses, and ultimately the formation of foam cells that drive atherosclerosis progression.
This research adds important detail to existing knowledge about atherosclerosis. Previous studies identified that mitochondrial dysfunction and oxidative stress contribute to artery disease, but this study pinpoints TRIM65 as a specific control switch that regulates these processes. The finding that TRIM65 inhibits mitophagy extends our understanding of how the TRIM protein family influences inflammation and immune responses, areas where these proteins were already known to play roles.
This study was conducted entirely in laboratory settings using mice and cultured cells, not in living humans. Mouse biology doesn’t always perfectly match human biology, so results may not directly apply to people. The study doesn’t specify the exact sample sizes for all experiments, making it harder to assess statistical power. Additionally, the research focuses on one specific protein pathway; atherosclerosis is a complex disease involving many different biological processes, so blocking TRIM65 alone may not be a complete solution. Long-term safety and effectiveness studies in humans would be necessary before any TRIM65-targeting drug could be used as a treatment.
The Bottom Line
Based on this research, TRIM65 emerges as a promising target for developing new atherosclerosis medications. However, current evidence is limited to laboratory studies. People concerned about heart disease should continue following established prevention strategies: maintaining a healthy diet low in saturated fats, exercising regularly, not smoking, and managing cholesterol and blood pressure through lifestyle changes or prescribed medications. Future TRIM65-targeting drugs may offer additional protection, but these are still in early research stages.
This research is most relevant to people at high risk for atherosclerosis, including those with family histories of heart disease, high cholesterol, high blood pressure, or diabetes. Cardiologists and researchers developing new heart disease treatments should pay close attention to these findings. The general population should understand that while this is promising basic science, it doesn’t yet translate to available treatments or lifestyle changes they should make today.
This research is in the early discovery phase. Typically, it takes 10-15 years from basic laboratory discoveries like this to develop and test new drugs in humans. If TRIM65-targeting medications are developed, they would need to go through multiple phases of human clinical trials before becoming available to patients. People should not expect new treatments based on this research to be available in the near future.
Frequently Asked Questions
What is TRIM65 and why does it matter for heart disease?
TRIM65 is a protein that controls whether cells can clean up damaged mitochondria. When TRIM65 is active, it blocks this cleanup process, causing toxic buildup that damages arteries. Blocking TRIM65 could prevent atherosclerosis development.
Can I reduce TRIM65 levels through diet or exercise?
Current research doesn’t show specific dietary or exercise interventions that reduce TRIM65. However, antioxidant-rich foods and regular exercise support mitochondrial health generally. Future TRIM65-targeting medications may offer more direct control.
When will TRIM65-targeting drugs be available for treating heart disease?
This is early-stage research. Typically, 10-15 years pass between laboratory discoveries and approved medications. TRIM65-targeting drugs would need extensive human testing before becoming available to patients.
Does this research mean I should change my cholesterol management approach?
No. Continue following your doctor’s recommendations for diet, exercise, and medications. This research identifies a future treatment target but doesn’t change current prevention strategies. Discuss any concerns with your healthcare provider.
How does TRIM65 cause foam cells that clog arteries?
TRIM65 blocks mitochondrial cleanup, causing damaged mitochondria to accumulate and generate harmful molecules called ROS. This oxidative stress triggers cells to absorb excessive cholesterol, transforming them into foam cells that build up in artery walls.
Want to Apply This Research?
- Users could track cardiovascular risk factors that relate to the biological processes this research describes: daily cholesterol intake (grams), oxidative stress markers through diet quality scores, and mitochondrial health indicators like exercise duration and intensity. Monitor these weekly to establish baseline patterns.
- Implement a high-antioxidant diet rich in foods that reduce oxidative stress (berries, leafy greens, nuts) and pair it with regular aerobic exercise, which improves mitochondrial function. Log meals and workouts daily to maintain consistency and see correlations with energy levels and cardiovascular markers.
- Create a 12-week tracking protocol measuring: weekly exercise minutes, daily antioxidant food servings, monthly cholesterol levels (if available), and subjective energy/fatigue ratings. This establishes whether lifestyle factors that support mitochondrial health correlate with personal wellness metrics, providing motivation while this research advances toward human applications.
This article summarizes laboratory research on atherosclerosis mechanisms and should not be interpreted as medical advice. The findings are based on studies in mice and cultured cells; human applications remain unproven. If you have concerns about heart disease, high cholesterol, or atherosclerosis risk, consult with a qualified healthcare provider. Do not modify your current medications, diet, or exercise regimen based on this research without medical guidance. TRIM65-targeting treatments are not yet available for human use.
This research translation is published by Gram Research, the science division of Gram, an AI-powered nutrition tracking app.