Limited macrophage positional dynamics in progressing or regressing murine atherosclerotic plaques-brief report

Jesse W. Williams, Catherine Martel, Stephane Potteaux, Ekaterina Esaulova, Molly A. Ingersoll, Andrew Elvington, Brian T. Saunders, Li Hao Huang, Andreas J. Habenicht, Bernd H. Zinselmeyer, Gwendalyn J. Randolph

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Objective-Macrophages play important roles in the pathogenesis of atherosclerosis, but their dynamics within plaques remain obscure. We aimed to quantify macrophage positional dynamics within progressing and regressing atherosclerotic plaques. Approach and Results-In a stable intravital preparation, large asymmetrical foamy macrophages in the intima of carotid artery plaques were sessile, but smaller rounded cells nearer plaque margins, possibly newly recruited monocytes, mobilized laterally along plaque borders. Thus, to test macrophage dynamics in plaques over a longer period of time in progressing and regressing disease, we quantified displacement of nondegradable phagocytic particles within macrophages for up to 6 weeks. In progressing plaques, macrophage-associated particles appeared to mobilize to deeper layers in plaque, whereas in regressing plaques, the label was persistently located near the lumen. By measuring the distance of the particles from the floor of the plaque, we discovered that particles remained at the same distance from the floor regardless of plaque progression or regression. The apparent deeper penetration of labeled cells in progressing conditions could be attributed to monocyte recruitment that generated new superficial layers of macrophages over the labeled phagocytes. Conclusions-Although there may be individual exceptions, as a population, newly differentiated macrophages fail to penetrate significantly deeper than the limited depth they reside on initial entry, regardless of plaque progression, or regression. These limited dynamics may prevent macrophages from escaping areas with unfavorable conditions (such as hypoxia) and pose a challenge for newly recruited macrophages to clear debris through efferocytosis deep within plaque. Visual Overview-An online visual overview is available for this article.

Original languageEnglish (US)
Pages (from-to)1702-1710
Number of pages9
JournalArteriosclerosis, thrombosis, and vascular biology
Volume38
Issue number8
DOIs
StatePublished - Jan 1 2018

Bibliographical note

Funding Information:
We thank D.J. Rader (University of Pennsylvania) for kindly providing ApoE-encoding adenoviral vector. We also thank Anton Kyrychenko for designing and drawing the graphical abstract. Major support for this work was supplied by National Institutes of Health (NIH) R01/R37 AI049653 and NIH RO1 HL118206 to G.J. Randolph. Additional support to G.J. Randolph includes NIH DP1DK109668. J.W. Williams was supported by NIH training grant 2T32DK007120-41, American Heart Association (AHA) grant 17POST33410473, and NIH K99HL138163. A. Elvington was supported by NIH training grant T32-HL07081-38 and B.H. Zinselmeyer was supported by AHA grant 16SDGG30480008.

Funding Information:
Major support for this work was supplied by National Institutes of Health (NIH) R01/R37 AI049653 and NIH RO1 HL118206 to G.J. Randolph. Additional support to G.J. Randolph includes NIH DP1DK109668. J.W. Williams was supported by NIH training grant 2T32DK007120-41, American Heart Association (AHA) grant 17POST33410473, and NIH K99HL138163. A. Elvington was supported by NIH training grant T32-HL07081-38 and B.H. Zinselmeyer was supported by AHA grant 16SDGG30480008.

Publisher Copyright:
© 2018 American Heart Association, Inc.

Keywords

  • Arteriosclerosis
  • Cell adhesion
  • Inflammation
  • Intravital microscopy
  • Monocytes

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Video-Audio Media

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