Figure 3.

Different subpopulations of neutrophils have distinct effects on collateral growth and angiogenesis post-ischemia. Angiogenesis post-ischemia stimulates the growth of new collateral vessel conduits, which helps partially perfuse the tissues and sustain tissue viability until recanalization and reperfusion. Middle cerebral artery occlusion is depicted with collateral vessel growth post-ischemia. Three subtypes of neutrophils, pro-inflammatory N1, protective N2, and pro-angiogenic neutrophils are recruited to the inflammatory site post-IS in response to hypoxic stimuli and fluid shear stress. During ischemic injury, hypoxic genes, including VEGF-A, CXCL12, and DAMPs are upregulated. VEGF-A is overly expressed in endothelial cells, which recruit N1 neutrophils and pro-angiogenic neutrophils into the circulation. The later wave of recruitment consists of both pro-angiogenic and N2 neutrophils that initiate collateral development via MMP-9 release. This prompts collaterals recruitment from adjacent vascular arteries. Resolution of inflammation is completed by efferocytosis of neutrophils by macrophages.