Scientists discovered that a protein called ACP5 plays a major role in making heart disease worse. Using mice and lab experiments, researchers found that when ACP5 levels are high, it causes immune cells in the heart to become more aggressive and damage themselves. When they blocked or removed ACP5, the heart disease improved significantly. This discovery could lead to new medicines that target ACP5 to help prevent or slow down heart disease in people.

The Quick Take

  • What they studied: Whether a protein called ACP5 causes heart disease to get worse, and if blocking it could help prevent heart disease
  • Who participated: Mice that were genetically modified to develop heart disease, plus immune cells grown in the laboratory
  • Key finding: Blocking ACP5 reduced heart disease damage by a large amount, while increasing ACP5 made the disease much worse. The protein works by changing how immune cells behave and causing them to self-destruct
  • What it means for you: This research suggests that new medicines targeting ACP5 might help prevent or slow heart disease, but human studies are still needed before any treatment could be available

The Research Details

This was a laboratory research study using multiple approaches. First, scientists studied mice that were bred to develop heart disease naturally. They measured ACP5 levels in these mice and found it was very high. Then they used a drug to block ACP5 and saw if it helped. They also created mice where ACP5 was removed only from immune cells to test if that specific change mattered. Finally, they grew immune cells in dishes and tested what happened when they increased or decreased ACP5 levels.

The researchers used advanced techniques to understand how ACP5 works. They identified which other proteins ACP5 interacts with and traced the chain of events that leads to disease. They measured markers of cell damage and death to understand the mechanism. This multi-layered approach helps confirm that ACP5 really is causing the problem, not just appearing alongside it.

This research approach is important because it moves from observation to proof of cause-and-effect. Simply finding that ACP5 is high in sick mice isn’t enough—the researchers had to show that removing it actually helps. By testing in both whole animals and isolated cells, they could understand both the big picture and the specific molecular details. This gives confidence that ACP5 is truly a driver of disease.

This study has several strengths: it uses multiple experimental approaches that all point to the same conclusion, it includes both animal and cell-based experiments, and it identifies the specific molecular pathway involved. The use of genetically modified mice where ACP5 is removed only from immune cells is particularly strong because it shows the effect is specific to those cells. However, this is still early-stage research in animals and cells, not yet tested in humans. The findings are promising but would need to be confirmed in human studies before any treatment could be developed.

What the Results Show

When mice ate a high-fat diet, ACP5 levels increased dramatically in their heart arteries and in immune cells. When researchers blocked ACP5 with a drug, the amount of plaque buildup in the arteries decreased significantly. When they removed ACP5 specifically from immune cells, the same improvement happened.

The key mechanism involves immune cells called macrophages. These cells can be either helpful or harmful depending on their type. ACP5 pushes them toward the harmful type (called M1) and away from the helpful type (called M2). When ACP5 was blocked or removed, more cells stayed in the helpful M2 form.

At the cellular level, ACP5 causes a type of cell death called ferroptosis, where cells damage themselves through iron-related processes. When ACP5 was high, cells had more iron buildup and more oxidative damage. When ACP5 was removed, cells had better protection against this damage and stayed healthier.

The research identified that ACP5 works through a specific pathway involving proteins called JAK2 and STAT3. When harmful cholesterol particles (ox-LDL) were present, they triggered this pathway and increased ACP5. The researchers also found that ACP5 interacts with another protein called VDAC3 that controls mitochondrial function. When ACP5 was high, mitochondria (the cell’s energy factories) became damaged and dysfunctional. Removing ACP5 restored mitochondrial health and increased protective antioxidant levels in cells.

ACP5 was previously known mainly for its role in cancer and bone disease, where high levels indicate poor outcomes. This is the first study to show ACP5’s role in heart disease. The findings fit with what scientists already know about how immune cell behavior drives heart disease progression. The specific pathway through JAK2 and STAT3 has been implicated in other inflammatory diseases, so this connection makes biological sense.

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 used a specific drug to block ACP5, but that drug might have other effects not measured here. The sample sizes for some experiments aren’t clearly reported. Most importantly, this is very early research—it shows ACP5 is important, but much more work would be needed to develop a safe and effective human treatment.

The Bottom Line

Based on this research, there is moderate evidence that blocking ACP5 could be a promising new approach to treating heart disease. However, this is preliminary laboratory evidence only. No one should change their current heart disease treatment based on this study. Current proven approaches like statins, exercise, and diet remain the best options. This research suggests scientists should pursue developing ACP5-blocking drugs for human testing.

This research is most relevant to people at risk for heart disease, cardiologists, and pharmaceutical researchers developing new treatments. People with existing heart disease should continue their current medical care. This is not yet a treatment option for patients. Researchers studying inflammation and immune function should also find this work interesting.

This is very early-stage research. Even if an ACP5-blocking drug is developed, it would typically take 5-10 years of testing before it could be available to patients. Any benefits would likely develop gradually as the drug reduces inflammation and plaque buildup over time.

Want to Apply This Research?

  • Track heart disease risk factors that are currently measurable: blood pressure, cholesterol levels (if tested), weight, and exercise minutes per week. These can be monitored while waiting for new treatments to be developed.
  • Use the app to build habits that reduce inflammation and support heart health: increase daily steps, track water intake, log servings of vegetables, and monitor sleep quality. These proven approaches work through similar immune-calming mechanisms.
  • Set up monthly check-ins to review cardiovascular health metrics. As new ACP5-targeting treatments become available in the future, users could track how their markers change. For now, focus on maintaining or improving current risk factors.

This research describes early-stage laboratory findings in mice and cells, not yet tested in humans. It does not represent a proven treatment for heart disease. Anyone with heart disease or at risk for heart disease should continue following their doctor’s current treatment plan and not make changes based on this research. This article is for educational purposes only and should not be considered medical advice. Consult with a healthcare provider before making any changes to diet, exercise, or medications.