Scavenger receptor CD36 directs nonclassical monocyte patrolling along the endothelium during early atherogenesis

Paola M. Marcovecchio, Graham D. Thomas, Zbigniew Mikulski, Erik Ehinger, Karin A.L. Mueller, Amy Blatchley, Runpei Wu, Yury I. Miller, Anh Tram Nguyen, Angela M. Taylor, Coleen A. McNamara, Klaus Ley, Catherine C. Hedrick

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Objective-Nonclassical monocytes (NCM) function to maintain vascular homeostasis by crawling or patrolling along the vessel wall. This subset of monocytes responds to viruses, tumor cells, and other pathogens to aid in protection of the host. In this study, we wished to determine how early atherogenesis impacts NCM patrolling in the vasculature. Approach and Results-To study the role of NCM in early atherogenesis, we quantifed the patrolling behaviors of NCM in ApoE-/- (apolipoprotein E) and C57BL/6J mice fed a Western diet. Using intravital imaging, we found that NCM from Western diet?fed mice display a 4-fold increase in patrolling activity within large peripheral blood vessels. Both human and mouse NCM preferentially engulfed OxLDL (oxidized low-density lipoprotein) in the vasculature, and we observed that OxLDL selectively induced NCM patrolling in vivo. Induction of patrolling during early atherogenesis required scavenger receptor CD36, as CD36-/- mice revealed a signifcant reduction in patrolling activity along the femoral vasculature. Mechanistically, we found that CD36-regulated patrolling was mediated by a SFK (src family kinase) through DAP12 (DNAX activating protein of 12KDa) adaptor protein. Conclusions-Our studies show a novel pathway for induction of NCM patrolling along the vascular wall during early atherogenesis. Mice fed a Western diet showed increased NCM patrolling activity with a concurrent increase in SFK phosphorylation. This patrolling activity was lost in the absence of either CD36 or DAP12. These data suggest that NCM function in an atheroprotective manner through sensing and responding to oxidized lipoprotein moieties via scavenger receptor engagement during early atherogenesis.

Original languageEnglish (US)
Pages (from-to)2043-2052
Number of pages10
JournalArteriosclerosis, thrombosis, and vascular biology
Issue number11
StatePublished - 2017
Externally publishedYes


  • Atherosclerosis
  • Humans
  • Mice
  • Monocytes
  • Phosphorylation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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