Researchers uncover how aging cells may trigger heart attacks and strokes

MD Anderson Research News June 03, 2026

• Some cancer treatments come with a risk of cardiovascular side effects, highlighting a need to understand underlying causes
• Researchers discovered a new molecular pathway that helps explain how disturbed blood flow contributes to the formation of dangerous, unstable atherosclerotic plaques
• Disturbed blood flow lowers the levels of protective proteins in blood vessel cells, which activates CD38 to promote blood vessel damage
• Study suggests CD38-targeted therapies could be a potential strategy to reduce the risk of plaque instability and cardiovascular disease

HOUSTON, JUNE 4, 2026 ― Researchers at The University of Texas MD Anderson Cancer Center have discovered a molecular pathway that drives certain stressed or aging cells to become abnormally active, causing inflammation inside blood vessel plaques. This results in disturbed blood flow and high-risk lesions that can lead to blood clots that cause heart attacks or strokes.

The findings, published in Circulation Research, may also help explain cardiovascular side effects seen with some cancer treatments, which can accelerate cellular aging. The study was co-led by Sivareddy Kotla, Ph.D., associate professor of Cardiology, and Jun-ichi Abe, M.D., Ph.D., professor of Cardiology.

The researchers studied senescent cells, which are stressed or aging cells that have stopped dividing but don’t die. They discovered that losing key regulatory proteins, LATS1/2, in these cells activates the CD38 enzyme, which reprograms how these cells use energy and makes them more unstable. This leads to inflammation and an increased risk of blood clot formation inside plaques, a process known as atherothrombosis.

“Our findings provide a previously unknown mechanistic link between senescence and thrombosis, which helps explain why some plaques can suddenly become dangerous,” Kotla said. “Understanding how aging cells rewire their surroundings and trigger plaque instability is essential for the development of therapeutic strategies that can reduce the risk of serious cardiovascular events.”

How did the researchers discover this key pathway?

The researchers used advanced molecular profiling on preclinical models to show how endothelial cells – the cells lining blood vessels – change with the loss of LATS1/2 proteins, which usually help with healthy cell stabilization. Removing LATS1/2 in endothelial cells caused them to become senescent but also abnormally active. This led to instability, leaky vessels, inflammation, abnormal vessel growth and plaques that could form clots, all of which are pro-thrombotic features.

Further analyses showed that these senescent cells had a dramatic increase in CD38 levels, highlighting their potential role as key drivers of this hybrid state. Preclinical models demonstrated that overexpressing CD38 rewired the metabolic pathways and energy sources for endothelial cells, leading them to consume enough additional energy to drive inflammation. This destabilized plaques and led to the formation of blood clots. Inhibiting CD38 reversed these effects both in vitro and in vivo.

What do these findings mean for patients?

While these results are still preclinical, the researchers were able to validate these findings using samples from human plaques and show that these samples share the same metabolic signatures and molecular pathways.

These findings also are of potential importance to patients undergoing cancer treatments. Many cancer treatments can cause senescence in both tumor cells and healthy tissues and generate a variety of side effects, including an increased risk of heart attacks, strokes and vascular inflammation. Understanding the underlying mechanisms may help researchers to better treat or prevent these side effects.

“These findings reveal an entirely new connection between blood flow patterns, cellular metabolism and vascular disease,” Abe said. “We hope this work will open new avenues for preventing plaque progression and thrombotic complications.”

The researchers point out that more studies are needed to explore potential biomarkers and targets, but this study provides a mechanistic rationale to encourage the exploration of CD38-targeted therapies in stabilizing plaques and reducing the risk of thrombosis. Interestingly, some CD38 inhibitors already are FDA-approved for other cancer types, suggesting that they might easily be repurposed.

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The study was supported by the National Institutes of Health (NIH), the Cancer Prevention and Research Institute of Texas (CPRIT) and institutional funding. For a full list of collaborating authors, disclosures and funding sources, see the full paper in Circulation Research.