Monocyte influx supports the proliferation of angiogenic microvessels under ischemic and inflammatory conditions

37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, SA95

Research Symposium: Monocyte influx supports the proliferation of angiogenic microvessels under ischemic and inflammatory conditions

A. Woodfin1, B. Ma1, S. Nourshargh1

1. William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom.

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Angiogenesis is a common feature of chronic inflammatory and ischemic conditions, and is both driven by, and contributory to, the eventual pathological outcomes. An example of this can be seen in the development of atherosclerotic plaques, where neovascularisation facilitates monocyte infiltration into lesions, a process that contributes to plaque instability and eventual rupture, leading to thrombosis and vascular occlusion. Yet despite the tremendous interest in the role of angiogenesis in these disorders surprisingly little is known about the profile, dynamics and mechanisms of inflammation within angiogenic tissues. A major limiting factor here has been the lack of availability of suitable in vivo models for direct investigations of inflammatory events in angiogenic vessels. We have developed a model of ischemic angiogenesis in the mouse cremaster, which is amenable to in vivo confocal imaging with high temporal and spatial resolution. This imaging system has been employed to characterise the angiogenic profile of this model and to investigate the link between immune cell infiltration and new vessel growth. At one week post induction of chronic ischemia, tissues exhibit a high density of small diameter, PECAM-1 expressing microvessels, with a functional lumen but a characteristically disordered morphology. A significant tissue infiltration of CX3CR1-eGFP+ cells of a monocytic lineage were noted at this time point, often forming close associations with angiogenic vessels. Further analysis of the time course of infiltration and phenotype of these CX3CR1-eGFP+ cells has revealed that a large influx of GR1high/F4/80low M1 type monocytes is seen within one day of induction of ischemia. Subsequently these cells migrate within the tissue and undergo morphological and phenotypic changes, adopting a GR1low/F4/80high M2 like macrophage phenotype by one week post ischemia. Depletion of blood monocytes prior to induction of ischemia significantly inhibits the angiogenic response, demonstrating a role for these cells in vasculogenesis. The present study into the relationship between myeloid cells and the induction and maintenance of chronic inflammation and angiogenesis aims to identify potential opportunities for therapeutic interventions in the context of chronic inflammatory and ischemic disorders.



Where applicable, experiments conform with Society ethical requirements.

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