Researchers discovered that a protein called clusterin may play a key role in developing heart disease, especially when people eat high-fat, high-cholesterol diets. Using pigs and mice, scientists found that this protein becomes more active in diseased arteries and triggers a chain reaction that damages blood vessels. This discovery could lead to new treatments that target this specific protein to prevent or slow down heart disease. The findings suggest that controlling clusterin levels might be a promising way to protect heart health in people who eat unhealthy diets.

The Quick Take

  • What they studied: Whether a protein called clusterin plays a role in causing atherosclerosis (hardening and narrowing of arteries) when animals eat high-fat, high-cholesterol diets
  • Who participated: The study used Bama miniature pigs and mice. The pigs were fed a high-cholesterol, high-fat diet to mimic how some people eat, while control animals ate normal diets
  • Key finding: Clusterin protein levels were significantly higher in diseased arteries compared to healthy ones. This protein appeared to activate a specific pathway (LRP1/AKT) that speeds up artery damage
  • What it means for you: This research suggests that if scientists can find ways to reduce clusterin in the body, it might help prevent or slow heart disease—especially for people who eat high-fat diets. However, this is early-stage research in animals, not yet proven in humans

The Research Details

Scientists created heart disease in pigs by feeding them a diet high in cholesterol and fat for a period of time. They then examined the diseased arteries and compared them to healthy arteries using advanced protein analysis techniques. This allowed them to identify which proteins were different between sick and healthy blood vessels. The researchers also studied mice to confirm their findings and used additional lab tests to understand exactly how the clusterin protein causes damage to arteries.

Using animal models before human studies is important because it allows scientists to safely test ideas and understand the biological mechanisms without risking human health. Pigs have cardiovascular systems similar to humans, making them good models for studying heart disease. This approach helps researchers identify specific targets for future medicines

The study used multiple validation methods (testing in both pigs and mice, using different laboratory techniques) which strengthens confidence in the findings. However, because this research was conducted only in animals and not yet in humans, the results cannot be directly applied to people yet. The journal publishes experimental medicine research, which is appropriate for this type of animal study

What the Results Show

When animals ate the high-fat, high-cholesterol diet, they developed atherosclerosis similar to human heart disease, with elevated cholesterol levels in their blood. The researchers identified 108 proteins that were different between diseased and healthy arteries. Among these, clusterin stood out as being significantly increased in the diseased tissue. Clusterin was particularly abundant in two types of cells that line and support blood vessels—endothelial cells and smooth muscle cells. The protein appeared to activate a specific cellular pathway called LRP1/AKT, which is known to promote artery damage and disease progression.

The study identified three other hub proteins involved in atherosclerosis, though clusterin was the primary focus. The research confirmed that the high-fat diet successfully created atherosclerotic changes in the animal models, validating their experimental approach. The findings were consistent across both pig and mouse models, suggesting the mechanism may be broadly applicable

While clusterin has been studied in other diseases, this research appears to be among the first to identify its specific role in promoting atherosclerosis through the LRP1/AKT pathway. Previous research has shown that this signaling pathway is important in heart disease, but the role of clusterin in activating it is relatively novel. The findings build on existing knowledge about how high-fat diets damage arteries at the molecular level

This research was conducted only in animals (pigs and mice), not in humans, so the results cannot yet be directly applied to people. The study did not test any treatments to reduce clusterin, so we don’t know if lowering it would actually prevent disease. The sample size of animals used was not specified in the abstract. Additionally, the study focused on diet-induced atherosclerosis and may not apply to other causes of heart disease

The Bottom Line

This research suggests that clusterin may be a promising target for future heart disease treatments, but it is too early to make specific recommendations for people. Anyone concerned about heart disease should continue following established advice: eat a healthy diet low in saturated fat and cholesterol, exercise regularly, maintain a healthy weight, and work with their doctor on preventive care. This research does not change current medical guidance

This finding is most relevant to people at high risk for heart disease, particularly those who eat high-fat, high-cholesterol diets. Researchers and pharmaceutical companies developing new heart disease treatments should pay attention to these findings. People with existing heart disease may eventually benefit if this research leads to new medicines. This research is not yet actionable for the general public

This is basic research that identifies a potential target. It typically takes 10-15 years from this type of discovery to develop and test a new medicine in humans. People should not expect treatments based on this finding to be available soon

Want to Apply This Research?

  • Track daily dietary fat and cholesterol intake (grams of saturated fat and milligrams of cholesterol) along with weekly blood lipid levels if available through home testing kits. This creates a personal record of how diet affects the risk factors for atherosclerosis
  • Users can set a goal to reduce saturated fat intake to less than 10% of daily calories and track progress weekly. The app could provide meal suggestions that are lower in cholesterol and fat while maintaining nutritional balance, helping users make dietary changes that may reduce atherosclerosis risk
  • Establish a long-term tracking system that monitors dietary patterns monthly and correlates them with available health markers (cholesterol levels from doctor visits, weight, exercise frequency). This helps users see the relationship between their lifestyle choices and cardiovascular risk factors over time

This research was conducted in animals and has not yet been tested in humans. The findings do not represent proven treatments or medical advice for people. Anyone concerned about heart disease should consult with their healthcare provider about prevention and treatment options. This article is for educational purposes only and should not replace professional medical advice. Do not make changes to your diet or medications based solely on this research without discussing with your doctor first.