When cells stop dividing but refuse to die, they can wreak havoc on the blood vessels that keep us alive—and researchers at The University of Texas MD Anderson Cancer Center in Houston have just uncovered how. In a study published in Circulation Research, scientists discovered that aging cells inside blood vessel plaques become dangerously overactive, triggering inflammation and blood clots that can suddenly cause heart attacks or strokes.
The discovery matters because plaques are already a leading cause of cardiovascular disease worldwide, but doctors have long struggled to predict which ones will rupture. Understanding what makes certain plaques unstable could reshape how we prevent and treat these life-threatening events. It may also explain why some cancer patients experience heart complications after treatment—a side effect that has puzzled researchers for years.
The study, co-led by associate professor Sivareddy Kotla and professor Jun-ichi Abe from the Department of Cardiology, focused on senescent cells: stressed or aging cells that have stopped dividing but don't undergo normal cell death. Using advanced molecular profiling on preclinical models, the researchers discovered that when these senescent cells lose two key regulatory proteins called LATS1 and LATS2, something unexpected happens. Instead of becoming dormant, the cells become abnormally active, ramping up production of an enzyme called CD38. This enzyme rewires how the cells use energy, making them consume additional power to fuel inflammation and destabilize the plaques around them.
The pathway they uncovered is strikingly specific. When LATS1/2 proteins vanish from endothelial cells—the cells lining blood vessels—those cells shift into a hybrid state: senescent yet hyperactive at the same time. The resulting inflammation creates leaky vessels, abnormal vessel growth, and most critically, plaques prone to forming blood clots, a process called atherothrombosis. When the researchers inhibited CD38 in their models, these dangerous effects reversed both in laboratory conditions and in living organisms.
What makes this finding clinically promising is that the researchers weren't working in a vacuum. They validated their preclinical findings using actual human plaque samples, confirming that those samples share the same metabolic signatures and molecular pathways. This is the bridge between basic science and real-world relevance that often determines whether a discovery will eventually help patients.
The implications extend beyond traditional heart disease. Many cancer treatments force cells into senescence as part of their tumor-fighting strategy, but this collateral effect on healthy tissue is a double-edged sword. It may explain why patients undergoing chemotherapy or other cancer therapies sometimes experience increased risk of heart attacks, strokes, and vascular inflammation. Understanding the mechanism opens a path to preventing these serious side effects.
Perhaps most intriguingly, some CD38 inhibitors are already FDA-approved for treating certain cancers. This suggests that existing drugs might be repurposed to stabilize plaques and reduce thrombosis risk—a possibility that could accelerate translation from lab to clinic. While the researchers emphasize that more work is needed to identify biomarkers and validate therapeutic targets, they've provided a mechanistic roadmap that could guide the next generation of cardiovascular treatments and help prevent the sudden, devastating events that plaques can trigger.