Macrophage activation and atherogenesis

This presentation was given by Andrew Newby, United Kingdom. It was presented at the ISN’s Forefronts Symposium 2015 taking place in Shenzhen, China, on October 22-25, 2015 for which the theme was ‘Immunomodulation of Cardio-Renal Function’ during Session 8: Immunity, Atherogenesis and Vascular Function.

 

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Presentation Abstract: 

Macrophages are present at all stages of human and experimental atherosclerosis. Forcing apoptosis of macrophages reduces early lipid deposition and deleting the major trophic cytokine CSF-1 greatly reduces atherosclerosis in mice. Hence, despite the ability of smooth muscle cells to adopt macrophage-like properties in the presence of oxidised-LDL, monocyte-derived macrophages are still believed to play the major role in foam cell formation and plaque progression. The positive relationship between levels of circulating monocyte populations and atherosclerosis susceptibility reinforces this conclusion.

It has been increasingly recognised that macrophages can provoke tissue injury or repair depending on the temporal and spatial distribution of local agonist factors. Pro-inflammatory lipids, cytokines, pattern or damage associated molecular patterns can act through a variety of distinct signalling pathways to generate so-called classically activated (shorthand M1) states. On the contrary, anti-inflammatory lipids and cytokines promote a variety of alternatively-activated (shorthand M2) states. Almost all of these occur in human and animal plaques at some stage of development. 

Although widely assfumed that M1 states promote plaque rupture and myocardial infarction, the evidence for this is only slowly accumulating. Moreover, the important mediators of macrophage activation are uncertain, which is a barrier to the development of appropriate treatments.  In this presentation, new data pointing to the relative importance of foam cell formation as a result of lipid accumulation, acquired and innate immunity will be critically appraised. Moreover, limitations of identifying precise mediators in human atherosclerosis and animal models will be discussed.

Production of matrix degrading enzymes is a key feature connecting macrophage activation to plaque instability. Both transcriptional and epigenetic regulation of protease production will be reviewed, together with recent evidence from population genetics that supports their importance. Finally, the prospects will be considered for new therapies targeted at macrophage activation or its consequences in order to prevent strokes and myocardial infarctions.

Additional Info

  • Language:
    English
  • Contains Audio:
    Yes
  • Content Type:
    Presentations
  • Source:
    ISN
  • Event:
    Forefronts
  • Year:
    2015
  • Members Only:
    No



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