As people grow older, changes occur throughout the body. Some cells become damaged by stress, disease, environmental exposures, or simply the aging process itself. Normally, damaged cells either repair themselves or die.
But some cells enter a state known as senescence, where they stop dividing but remain alive. Scientists have become increasingly interested in these aging cells because they appear to contribute to many chronic diseases.
A new study from researchers at The University of Texas MD Anderson Cancer Center suggests that these aging cells may play a surprisingly important role in heart disease.
The findings, published in Circulation Research, reveal how certain senescent cells can create conditions that make artery plaques more unstable and more likely to trigger dangerous blood clots.
Heart disease often begins when fatty deposits accumulate inside artery walls. Over time, these deposits form plaques. Some plaques remain relatively harmless, while others become inflamed and unstable.
When an unstable plaque ruptures, a blood clot can quickly form. If the clot blocks blood flow to the heart, it can cause a heart attack. If it blocks blood flow to the brain, it can cause a stroke.
Doctors have known for many years that inflammation plays an important role in this process. However, the exact biological mechanisms that transform a stable plaque into a dangerous one have remained unclear.
To investigate this question, researchers studied endothelial cells, which line the inside surface of blood vessels. These cells normally help regulate blood flow, prevent unwanted clotting, and maintain healthy blood vessel function.
The scientists focused on two proteins known as LATS1 and LATS2. Under normal conditions, these proteins help maintain healthy cellular behavior. When the researchers removed these proteins, the endothelial cells entered a senescent state. Instead of becoming inactive, however, the cells became highly disruptive.
The altered cells produced inflammation, weakened blood vessel integrity, and encouraged conditions associated with clot formation. Blood vessels became leakier, and abnormal growth of new blood vessels was observed. These changes created a setting in which artery plaques became increasingly unstable.
The team then searched for the mechanism behind these effects. Their investigation led them to an enzyme called CD38. Levels of CD38 increased dramatically in the senescent cells. The enzyme changed the way cells generated energy, forcing them into a highly active metabolic state that fueled inflammation.
In simple terms, the aging cells appeared to rewire their internal energy systems in a way that promoted damage rather than repair. This increased inflammation within plaques and made blood clot formation more likely.
The discovery became even more significant when researchers blocked CD38. Doing so reversed many of the harmful changes seen in laboratory experiments and animal models. This suggests that targeting CD38 may help prevent plaque instability and reduce the risk of dangerous cardiovascular events.
The researchers strengthened their findings by examining human plaque samples. These samples showed many of the same molecular signatures observed in the experimental studies, increasing confidence that the pathway is relevant to human disease.
The study may also help explain a long-standing problem in cancer care. Some cancer treatments can accelerate cellular aging, leading to increased numbers of senescent cells.
Patients receiving these therapies sometimes develop cardiovascular complications, including vascular inflammation and elevated risks of heart attacks or strokes. The newly identified pathway may provide insight into how these side effects develop.
An exciting aspect of the discovery is that CD38 is already a target in cancer treatment. Several FDA-approved drugs currently block CD38 for specific blood cancers. Researchers hope that these existing medications might eventually be adapted to help protect cardiovascular health as well.
While the study does not yet prove that CD38 inhibitors can prevent heart attacks or strokes in humans, it provides a strong scientific rationale for future clinical trials. If successful, such therapies could represent an entirely new approach to treating cardiovascular disease by targeting aging cells and their harmful effects.
If you care about heart health, please read studies about top foods to love for a stronger heart, and why oranges may help fight obesity, diabetes, and heart disease.
For more health information, please see recent studies about simple guide to a 7-day diabetes meal plan, and why you should add black beans to your plate.
Source: The University of Texas MD Anderson Cancer Center.
