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Billions of peripheral white blood cells are produced daily by the regular division of haematopoietic stem cells and their offspring in the bone marrow. Under normal circumstances, thousands of stem cells contribute offspring to the blood at one point, making white blood cells a group with different ancestors.

Clonal hematopoiesis is a common age-related disease in which the offspring of one of these hematopoietic stem cells begin to dominate significant parts of the blood. Genome-wide analyzes have shown that clonal hematopoiesis is often triggered by recurring genetic changes that give certain hematopoietic stem cells a competitive advantage and thus give them the ability to expand disproportionately.

Several independent studies have shown that clonal hematopoiesis is often associated with atherosclerosis and cardiovascular disease. Since its discovery, this surprising association has attracted great interest from both clinicians and researchers.

Cardiovascular diseases are the leading cause of morbidity and mortality in Western countries and pose a massive public health burden. Do blood clonal expansions contribute to the progression of atherosclerosis, and if so, how?

Subsequent work showed that the formation of atherosclerotic plaques can actually be increased by immune cells with clonal hematopoiesis-related mutations, which raises the question of whether clonal expansions in the blood should be used therapeutically to prevent cardiovascular diseases.

In a new study published in Cell, researchers at Massachusetts General Hospital and Harvard Medical School are now suggesting another, additional possibility: atherosclerosis causes clonal hematopoiesis. Patients with atherosclerosis suffer from hyperlipidemia and inflammation, two conditions known to chronically increase rates of haematopoietic stem cell division. In the new study, the researchers now show that this increased division accelerates the development of clonal hematopoiesis.

Kamila Naxerova, Ph.D., principal researcher at the MGH Center for Systems Biology and lead author on the study, says, “Patients with atherosclerosis essentially experience an ‘accelerated time’. This is because the rate at which genetic changes occur and spread in the hematopoietic system, determined by the underlying rate of stem cell division. From a genetic point of view, atherosclerosis could be said to accelerate the aging of the blood. Since clonal hematopoiesis is an age-related disease, atherosclerosis patients tend to develop it earlier as healthy people, “says Naxerova, who is also an assistant professor of radiology at Harvard Medical School.

Naxerova says her team’s findings may be good news for patients with clonal hematopoiesis: “There is no doubt that more research is needed to carefully examine the link between clonal hematopoiesis and cardiovascular disease. Our results however, suggest that clonal hematopoiesis may occur in some cases is just a relatively harmless sign of an overactive hematopoietic system and not a hazard in itself. “

“What makes this study unique is that the interdisciplinary team used mathematical models to discover a new paradigm in the field of atherosclerosis and to further elucidate the interplay between cardiovascular disease and clonal hematopoiesis,” says Michelle Olive, Ph. D., Program Officer in the Department of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute, part of the National Institutes of Health.

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More information:
Alexander Heyde et al., Increased Stem Cell Proliferation in Atherosclerosis Accelerates Clonal Hematopoiesis, Cell (2021). DOI: 10.1016 / j.cell.2021.01.049

Journal information:
Cell provided by Massachusetts General Hospital

Quote: Atherosclerosis May Accelerate the Development of Clonal Hematopoiesis, Study Results (2021, February 26), accessed on February 27, 2021 from

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