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Monocyte Recruitment during Microvascular Arteriogenesis is Induced by Altered Flow and Influenced by Proximity of Venules to Collateral Arterioles

It has previously been shown that monocyte recruitment is required for arteriogenesis in large diameter collateral arteries following elevated shear stress induced by occlusion. Once recruited to the stimulated collateral vessel, these cells promote smooth muscle cell and endothelial cell proliferation through secreted cytokines. However, this recruitment has not been clearly demonstrated in collateral arterioles (≤100 microns in diameter) of the microcirculation and questions remain regarding the route by which these cells arrive (egress from arteriole vs. venule) in the microcirculation. We utilize laser speckle flowmetry to measure relative changes in blood flow velocity experienced by individual arteriole collaterals in the murine spinotrapezius muscle and ear following feeder arteriole occlusion. In addition, the effect of network architecture on these flow changes is investigated. Localized recruitment of fluorescent protein‐expressing monocytes in the CX3CR1‐eGFP transgenic mouse is observed around the mural cell layer of NG2+ collateral arterioles 3 days post‐ligation. Moreover, the orientation of venules in relation to shear‐activated collateral arterioles appears to influence which sites along the collateral arteriole remodel following elevated shear stress. Our results suggest that monocyte recruitment to remodeling collaterals following small arteriole occlusion is a result of altered blood flow and occurs preferentially at collateral sites which are in close proximity to a paired venule. Funding provided by NIH‐HL082838‐02.