How cardiovascular diseases disturb the bone marrow microenvironment

In the inaugural issue of the new journal Nature group journal Nature Cardiovascular Research released in January 2022, the Nahrendorf lab sheds light on a novel regulatory loop between the bone marrow and the cardiovascular system. It is increasingly recognized that an oversupply of myeloid cells from the bone marrow into the blood promotes atherosclerosis and heart failure, while the mechanisms that disturb the homeostatic regulation of leukocyte production (hematopoiesis) in the bone marrow are not yet fully understood. Hematopoiesis occurs in a specialized microenvironment (niche) in the bone marrow with different niche cells. Among these, bone marrow endothelial cells are important regulators of hematopoietic stem cell maintenance and expansion in the niche. In this highlighted publication, Rohde et al. use various mouse models of cardiovascular disease (hypertension, atherosclerosis and myocardial infarction (MI)) to study alterations in the bone marrow vasculature. Using intravital imaging of the bone marrow and complementary analyses, the authors elegantly show that cardiovascular diseases lead to endothelial dysfunction, increased integrin abundance, compromised barrier function, and angiogenesis in the bone marrow microcirculation. Transcriptomic analysis and cell-specific knockout models identified a role for endothelial VEGF receptor 2, the cytokine IL-6 and the proteoglycan versican in this dysregulation. In conclusion, this study establishes a novel crosstalk between diseased arteries, the heart and the bone marrow. In the future, it will be important to study the clinical implications of these observations and whether e.g. local anti-inflammatory strategies to restore the bone marrow endothelial niche homeostasis could be an efficient way to treat high-risk cardiovascular disease patients with leukocytosis.