Myeloid cell contributions to cardiovascular health and disease

Abstract

Recent advances in cell tracing and sequencing technologies have expanded our knowledge on leukocyte behavior. As a consequence, inflammatory cells, such as monocyte-derived macrophages, and their actions and products are increasingly being considered as potential drug targets for treatment of atherosclerosis, myocardial infarction and heart failure. Particularly promising developments are the identification of harmful arterial and cardiac macrophage subsets, the cells' altered, sometimes even clonal production in hematopoietic organs, and epigenetically entrained memories of myeloid progenitors and macrophages in the setting of cardiovascular disease. Given the roles of monocytes and macrophages in host defense, intricately understanding the involved cellular subsets, sources and functions is essential for the design of precision therapeutics that preserve protective innate immunity. Here I review how new clinical and preclinical data, often linking the cardiovascular, immune and other organ systems, propel conceptual advances to a point where cardiovascular immunotherapy appears within reach.

Figure 1:. Hematopoiesis and CVD.

The cartoon summarizes interaction of risk factors for CVD and changes in innate immune supply that promote inflammation in the cardiovascular system.

Figure 2:. The hematopoietic niche and CVD.

The cartoon summarizes interaction of risk factors with the hematopoietic stem cell niche that senses systemic danger and regulates production of CVD-promoting leukocytes.

Figure 3:. Clonal hematopoiesis.

A driver mutation, for instance in the gene Tet2, leads to expansion of a hematopoietic stem cell (HSC) clone, which gives rise to a variably sized leukocyte clone in circulation. Clonal hematopoiesis associates with higher incidence of MI in patients^,. In mice, Tet2 deletion leads to larger, more inflamed plaques^, and impaired recovery from acute MI.