Heart attacks and strokes remain leading causes of death globally. These conditions are often associated with atherosclerosis, a process where fatty deposits called plaques accumulate inside arteries.
As time passes, these plaques can constrict blood vessels, limiting blood flow. It has been understood for some time that not all plaques pose the same threat. Some stay stable for years, while others suddenly become unstable, rupture, and trigger blood clots that can block blood flow to the heart or brain.
A recent study from The University of Texas MD Anderson Cancer Center offers new insights into why some plaques turn more dangerous. Published in Circulation Research, the research identified a molecular pathway that seems to promote inflammation and clot formation within artery plaques.
The study zeroed in on a specific group of cells called senescent cells—cells that have become stressed or aged. Unlike normal cells, senescent cells stop dividing but do not die off. Instead, they remain in tissues and can influence neighboring cells. Increasing evidence links these aging cells to diseases such as cancer, heart disease, and age-related conditions.
The research team aimed to determine how senescent cells impact blood vessels and plaque buildup. They focused on endothelial cells, which line the inside of blood vessels, helping regulate blood flow and maintain vessel stability. The scientists found that removing two key proteins, LATS1 and LATS2, caused endothelial cells to change significantly. Instead of staying stable, these cells entered a senescent-like state but became unusually active.
This cellular shift promoted inflammation, made blood vessels leakier, stimulated abnormal new vessel growth, and created conditions conducive to clot formation. Further investigation revealed these effects were linked to a notable increase in an enzyme called CD38. This enzyme appears to reprogram cellular energy production, leading cells to consume more energy and shift into a pro-inflammatory, destabilized state.
This environment made plaques more prone to rupture and blood clot development. The study identified CD38 as a central driver behind this harmful process. Importantly, blocking CD38 activity reversed many of these effects. In both lab tests and animal models, inhibiting CD38 reduced inflammation and enhanced plaque stability. These results point to CD38 as a promising target for new treatments.
One encouraging aspect is that some drugs targeting CD38 are already approved by the FDA for certain types of cancer. This existing approval could accelerate efforts to explore their use for cardiovascular issues without needing to develop new medications from scratch.
Researchers also examined human plaque samples, observing similar molecular patterns, which suggests these mechanisms are relevant to humans, not just experimental models. The findings may be especially significant for cancer patients, as many cancer therapies accelerate cellular aging and increase senescent cell counts. Some individuals undergoing treatment experience higher rates of heart attacks, strokes, and blood vessel inflammation. The newly identified pathway could help explain these side effects.
Understanding how senescent cells affect blood vessel health offers potential opportunities to prevent cardiovascular disease. By targeting the molecular processes that weaken plaques, future therapies might lower the risk of dangerous blood clots that can cause life-threatening events.
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Source: The University of Texas MD Anderson Cancer Center.