Reprogramming of bone marrow myeloid precursor cells in patients with severe coronary artery disease

Cardiovascular diseases, such as stroke or myocardial infarction, are caused by the narrowing and closure of arteries by plaques, as a result of a process called atherosclerosis. Important risk factors for atherosclerosis are high cholesterol, high blood pressure, diabetes and obesity.

Our innate immune system plays an important role in the development of these plaques via chronic inflammation, and previous research has shown that drugs which inhibit inflammation can indeed reduce the occurrence of cardiovascular diseases.

Zooming in on the immune system in atherosclerosis

Macrophages are important immune cells from the innate immune system, and the most common type of immune cells in atherosclerotic plaques. They are derived from another cell type - monocytes - that is present in the blood. In patients with cardiovascular disease, these monocytes are more active, producing more inflammatory molecules than in healthy individuals. It is not yet clear how these monocytes are activated in patients with cardiovascular disease.

In this study, published in eLife, a small group of 13 patients with coronary heart disease, due to severe coronary atherosclerosis, was compared to a group of 13 patients without atherosclerosis. In these study participants a bone marrow puncture was performed so that the researchers could isolate and study the residing stem cells. These stem cells are the precursor cells of all blood cells, including the monocytes. The researchers showed that in patients with atherosclerosis, these precursor cells were programmed differently, so that they produced more activated monocytes.

What does this mean for our knowledge of the immune system and future treatments?

This study adds an extra dimension to the role of the immune system in the development of cardiovascular diseases by showing that activation of this system takes place at the level of precursor cells in the bone marrow.

Niels Riksen, theme Vascular damage and last author of the article: 'This finding could explain how risk factors for cardiovascular disease, such as high cholesterol or obesity, can have a long-term effect on the immune system. In addition, this knowledge is relevant and important for the development of new drugs targeting the immune system for the treatment or prevention of cardiovascular diseases'.

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