Endothelial Protective Monocyte Patrolling in Large Arteries Intensified by Western Diet and Atherosclerosis

Quintar, Amado A.; McArdle, Sara; Wolf, Dennis; Márki, Alex; Ehinger, Erik; Vassallo, Melanie; Miller, James; Mikulski, Zbigniew; Ley, Klaus; Buscher, Konrad

doi:10.1161/circresaha.117.310739

Cited by 88 publications

(99 citation statements)

References 40 publications

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“…Previous studies 24,37 have shown that LFA-1 and VLA-4 integrins mediate patrolling, particularly in atherosclerotic mice. It has been proposed that G αi chemokine receptors are necessary for inducing patrolling in NCM during inflammation 36 .…”

Section: Discussionmentioning

confidence: 91%

Scavenger Receptor CD36 Directs Nonclassical Monocyte Patrolling Along the Endothelium During Early Atherogenesis

Marcovecchio

Thomas

Mikulski

et al. 2017

ATVB

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Objective Nonclassical monocytes 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 nonclassical monocyte patrolling in the vasculature. Approach and Results To study the role of nonclassical monocytes in early atherogenesis, we quantified the patrolling behaviors of nonclassical monocytes in ApoE−/− and C57Bl/6J mice fed a Western diet. Using intravital imaging, we found that nonclassical monocytes from Western diet fed mice display a 4-fold increase in patrolling activity within large peripheral blood vessels. Both human and mouse nonclassical monocytes preferentially engulfed oxidized LDL in the vasculature, and we observed that oxidized LDL selectively induced nonclassical monocyte patrolling in vivo. Induction of patrolling during early atherogenesis required scavenger receptor CD36, as CD36−/− mice revealed a significant reduction in patrolling activity along the femoral vasculature. Mechanistically, we found that CD36-regulated patrolling was mediated by a Src family kinase (SFK) through DAP12 adaptor protein. Conclusions Our studies show a novel pathway for induction of nonclassical monocyte patrolling along the vascular wall during early atherogenesis. Mice fed a Western diet showed increased nonclassical monocyte 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 nonclassical monocytes function in an atheroprotective manner through sensing and responding to oxidized lipoprotein moieties via scavenger receptor engagement during early atherogenesis.

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Section: Discussionmentioning

confidence: 91%

Scavenger Receptor CD36 Directs Nonclassical Monocyte Patrolling Along the Endothelium During Early Atherogenesis

Marcovecchio

Thomas

Mikulski

et al. 2017

ATVB

Self Cite

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“…Howev er, most studies describing leukocyte recruitment have drawn conclusions from microcirculation, and more investigations are needed to confirm those findings in the macrocirculation. Nevertheless, the patrolling monocyte velocity is higher in the macrocirculation compared to the microcirculation, and it has been shown that monocyte adhesion to dysfunctional endothelium in large arteries is dependent on integrin-interactions [26]. The most abundant cells in atherosclerotic lesions are monocytes, macrophages, and smooth muscle cells (SMC).…”

Section: Mechanisms Of Arterial Leukocyte Entrymentioning

confidence: 99%

The Ins and Outs of Myeloid Cells in Atherosclerosis

Schumski¹,

Döring²,

Soehnlein³

2018

J Innate Immun

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Atherosclerosis is a chronic inflammation of the arterial vessel wall that arises from an imbalanced lipid metabolism. A growing body of literature describes leukocyte recruitment as a critical step in the initiation and progression of lesion development. By contrast, the role of leukocytes during plaque regression has been described in less detail. Leukocyte egress might be an important step to resolving chronic inflammation and therefore it may be a promising target for limiting advanced lesion development. This review aims to summarize our current knowledge of leukocyte recruitment to the arterial vessel wall. We will discuss mechanisms of leukocyte egress from the lesion site, as well as potential therapeutic strategies to promote atherosclerotic regression.

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“…In atherosclerosis, the real attachment of patrolling monocytes to the endothelium was observed. These data indicate that patrolling monocytes can be recruited to the atherosclerotic endothelium in a CX3CR1‐independent manner . In summary, CCR2, CX3CR1 and CCR5 play independent and additive roles in atherogenesis.…”

Section: High‐cholesterol Levels Increase Chemokine Signallingmentioning

confidence: 77%

“…Recently, Quintar with co‐authors employed a new method, long‐term 2‐photon intravital microscopy, to assess the behaviour and frequency of patrolling CX3CR1 high Ly6C low monocytes in live CX3CR1 + / GFP (green fluorescent protein) mice . The numbers of patrolling monocytes became increased by ninefold in CX3CR1‐GFP (green fluorescent protein) mice and by 22‐fold in CX3CR1 +/GFP /apoE‐deficient mice fed on cholesterol‐rich diet.…”

Section: High‐cholesterol Levels Increase Chemokine Signallingmentioning

confidence: 99%

“…Ly6C low monocytes dampen inflammation by releasing IL‐10, an anti‐inflammatory cytokine and differentiate to M2 macrophages after extravasation to the tissue . Patrolling Ly6C low monocytes possess a vasculoprotective function as depletion of this population in NR4A1/apoE‐deficient mice was shown to lead to massive apoptosis of arterial endothelial cells .…”

Section: Nr4a1‐deficient Animal Modelmentioning

confidence: 99%

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The role of monocytosis and neutrophilia in atherosclerosis

Chistiakov

Grechko

Myasoedova

et al. 2018

J Cellular Molecular Medi

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Monocytosis and neutrophilia are frequent events in atherosclerosis. These phenomena arise from the increased proliferation of hematopoietic stem and multipotential progenitor cells (HSPCs) and HSPC mobilization from the bone marrow to other immune organs and circulation. High cholesterol and inflammatory signals promote HSPC proliferation and preferential differentiation to the myeloid precursors (i.e., myelopoiesis) that than give rise to pro‐inflammatory immune cells. These cells accumulate in the plaques thereby enhancing vascular inflammation and contributing to further lesion progression. Studies in animal models of atherosclerosis showed that manipulation with HSPC proliferation and differentiation through the activation of LXR‐dependent mechanisms and restoration of cholesterol efflux may have a significant therapeutic potential.

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Endothelial Protective Monocyte Patrolling in Large Arteries Intensified by Western Diet and Atherosclerosis

Abstract: Supplemental Digital Content is available in the text.

Cited by 88 publications

References 40 publications

Scavenger Receptor CD36 Directs Nonclassical Monocyte Patrolling Along the Endothelium During Early Atherogenesis

Scavenger Receptor CD36 Directs Nonclassical Monocyte Patrolling Along the Endothelium During Early Atherogenesis

The Ins and Outs of Myeloid Cells in Atherosclerosis

The role of monocytosis and neutrophilia in atherosclerosis

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