A culprit cell that drives plaque buildup in arteries
Aging macrophages contribute to both early and late stages of atherosclerosis, the most common driver of cardiovascular disease, a new study in mice reveals. At early stages of the disease, removing these old or "senescent" cells caused regression of the atherosclerotic lesions, and at advanced stages, it limited disease progression, hinting at a potential cellular target for therapy. Atherosclerosis is the buildup of plaque within the arteries, which can restrict blood flow. If plaques rupture, they can cause blood clots that lead to a heart attack or other cardiovascular complications. Previous studies had linked plaque buildup with markers of cell senescence — a state whereby cells stop dividing but do not die – but it was unclear whether and when senescent cells actively contribute to the disease. To explore the role of senescent cells in more detail, Bennett Childs and colleagues studied atherosclerosis-prone mice that were genetically engineered in a way that allowed researchers to selectively eliminate senescent cells by administering a certain drug. When these mice were fed a high-fat diet and treated with the drug to remove senescent cells, they exhibited 60% less plaque compared to controls, despite similar feeding habits and blood lipids. By looking closely at the arteries of mice very shortly after starting a high-fat diet, the researchers observed fatty streaks containing lipid-filled "foamy" macrophages along the interior, which drove the expression of inflammatory cytokines. In mice with suppressed senescence, by contrast, these fatty streaks were reduced. Advanced atherosclerosis is characterized by unstable plaques that are prone to rupture; when the researchers studied mice with this advanced stage of disease, they found that markers of plaque instability were reduced in the mice with suppressed senescence compared to controls. These results suggest that blocking senescence could have beneficial effects at both early and late stages of atherosclerosis.
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