High Levels of Acetylated Low Density Lipoprotein Uptake and Low Tie2 Promoter Activity Distinguishes Sinusoids from Other Vessel Types in the Murine Bone Marrow

Background: The bone marrow contains a variety of blood vessels that have different functions in maintaining the bone marrow as the major blood producing organ in adulthood. For instance, arterioles function to control the flow of blood into bone marrow compartments, and the sinusoids serve as a conduit to the blood stream and niches for megakaryocyte development. Most current studies of the bone marrow vasculature, including studies quantifying changes in the marrow vascular by microvascular density, do not differentiate between different types of marrow vessels. Recognizing the changes in different types of blood vessels has important physiologic implications. Here we report a new method to distinguish sinusoids from arterioles in the murine bone marrow. Methods and Results: We used transgenic mice with GFP expressed downstream of the Tie-2 promoter, combined with in vivo acetylated low-density lipoprotein (Ac-LDL) uptake method to differentiate sinusoids from arterioles. We found that Ac-LDL was specifically endocytosed by sinusoids, and Tie-2 expression was more pronounced in the arteries, arterioles, and transitional capillaries. Combining these two functional endothelial markers and using confocal microscopy to obtain three dimensional images, we identified transitional zones where arterioles emptied into the sinusoids. Conclusions: These results demonstrate that the marrow vasculature and specific endothelial cell types are functionally heterogeneous. Methods to study changes in the marrow vasculature and particularly the vascular niche, a function of sinusoids, need to take into account this heterogeneity.