Cited by 109Atherosclerosis and Cardiovascular DiseasesCell Adhesion Molecules ResearchNeuroinflammation and Neurodegeneration Mechanisms

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

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Quintar, Amado, McArdle, Sara, Wolf, Dennis, Marki, Alex, Ehinger, Erik, Vassallo, Melanie, Miller, Jacqueline, Mikulski, Zbigniew +2 more·2017·Circulation Research

Abstract

Rationale: Nonclassical mouse monocyte (CX3CR1 high , Ly-6C low ) patrolling along the vessels of the microcirculation is critical for endothelial homeostasis and inflammation. Because of technical challenges, it is currently not established how patrolling occurs in large arteries. Objective: This study was undertaken to elucidate the molecular, migratory, and functional phenotypes of patrolling monocytes in the high shear and pulsatile environment of large arteries in healthy, hyperlipidemic, and atherosclerotic conditions. Methods and Results: Applying a new method for stable, long-term 2-photon intravital microscopy of unrestrained large arteries in live CX3CR1-GFP (green fluorescent protein) mice, we show that nonclassical monocytes patrol inside healthy carotid arteries at a velocity of 36 μm/min, 3× faster than in microvessels. The tracks are less straight but lead preferentially downstream. The number of patrolling monocytes is increased 9-fold by feeding wild-type mice a Western diet or by applying topical TLR7/8 (Toll-like receptor) agonists. A similar increase is seen in CX3CR1 +/GFP /apoE −/− mice on chow diet, with a further 2- to 3-fold increase on Western diet (22-fold over healthy). In plaque conditions, monocytes are readily captured onto the endothelium from free flow. Stable patrolling is unaffected in CX3CR1-deficient mice and involves the contribution of LFA-1 (lymphocyte-associated antigen 1) and α 4 integrins. The endothelial damage in atherosclerotic carotid arteries was assessed by electron microscopy and correlates with the number of intraluminal patrollers. Abolishing patrolling monocytes in Nr4a1 −/− apoE −/− mice leads to pronounced endothelial apoptosis. Conclusions: Arterial patrolling is a prominent new feature of nonclassical monocytes with unique molecular and kinetic properties. It is highly upregulated in hyperlipidemia and atherosclerosis in a CX3CR1-independent fashion and plays a potential role in endothelial protection.

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Crossref · 10.1161/circresaha.117.310739

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  • Nonclassical monocytes also patrol large-artery endothelium, and this patrolling is strongly increased in hyperlipidaemia and atherosclerosis, improving endothelial protection in the inflamed, high-shear, pulsatile environment of developing lesions.

    “However, a 2017 study in mice revealed that these nonclassical monocytes also patrol the endothelium of large arteries, and this type of arterial patrolling is highly upregulated in hyperlipidaemia and atherosclerosis, thereby allowing improved protection of the arterial endothelium in the inflamed, high-shear stress and pulsatile environment of a developing atherosclerotic lesion146.”

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Authors
Quintar, A., McArdle, S., Wolf, D., Marki, A., Ehinger, E., Vassallo, M., Miller, J., Mikulski, Z., Ley, K., & Buscher, K.
Affiliations
  • La Jolla Institute for Immunology (US)
  • From the La Jolla Institute for Allergy and Immunology, Division of Inflammation Biology, La Jolla, CA (A.Q., S.M., D.W., A.M., E.E., M.V., J.M., Z.M., K.L., K.B.); and Centro de Microscopia Electronica, INICSA-CONICET, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Cordoba, Argentina (A.Q.).
Corresponding author
  • Ley, Klaus
  • Buscher, Konrad
Venue
Circulation Research
Published
2017-05-26
Volume
120
Issue
11
Pages
1789-1799
ISSN
  • 0009-7330 (ISSN-L)
  • 1524-4571
OpenAlex
W2597243982
Cited by
109
References
37
Citations by year
2026: 7 · 2025: 8 · 2024: 14 · 2023: 4 · 2022: 9 · 2021: 17 · 2020: 13 · 2019: 7 · 2018: 22 · 2017: 8
FWCI
6.18
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Circulation Research (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Americanae (AECID Library) (submittedVersion, cc-by-nc-nd)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
Funders
National Heart, Lung, and Blood Institute (R01HL115232, T32HL105373)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
non-classical monocytes, CX3CR1, endothelial homeostasis, atherosclerosis, Western diet, hyperlipidemia, large arteries, carotid artery, endothelial injury, endothelial cell apoptosis, Nur77, LFA-1, CD49d, TLR agonists, monocyte migration, intravital microscopy
MeSH terms
CX3C Chemokine Receptor 1, Animals, Arteries, Endothelium, Vascular, Mice, Inbred C57BL, Monocytes, Mice, Knockout, Receptors, Chemokine, Atherosclerosis, Mice, Diet, Western

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